Ammonia

Definition and Structure The definitions, structures, and functions in cosmetics of Phosphoric Acid and its salts are presented in Table 1. Phosphoric Acid and its salts all have the same phosphate core. Except for Phosphoric Acid and Metaphosphoric Acid, the ingredients in this report are either alkaline earth metal (Periodic Table column I or II) salts or ammonium salts of a phosphoric acid. These ingredients are related to each other as inorganic phosphates, with varying cation identity and degree of protonation. This group comprises phosphate salts for which property differences are attributable primarily to having different cation(s). Characterizing these differences in one report that addresses all of these ingredients is more informative than attempting to assess the safety of these salts in separate reports that each addresses only one ingredient.  Distributed for comment only -- do not cite or quote Phosphoric Acid is a polyprotic acid which is deprotonated to mono-, di-, and tri-phosphates with rising pH. Figure1. Phosphoric Acid and the ortho-phosphates (dihydrogen phosphate, hydrogen phosphate, and phosphate) However, Phosphoric Acid and phosphate salts also exist as dimers and trimers of phosphate, pyro- and meta- respectively. Accordingly, these ingredients vary by the identity of associated cations, degree of protonation, and in the number of phosphate repeat units (i.e., 1 repeat is ortho-, 2 repeats is pyro-, and 3 repeats is meta-). Figure 2. Dehydration of phosphoric acids, from ortho- to pyro- to meta-phosphoric acid. As some of the Dictionary names for these ingredients vary from the customary names and may be confusing, systematic names have been, where appropriate, added to Table 1. However, elsewhere in this report only the Dictionary ingredient name is used. Chemical and Physical Properties … [kırpıldı — bölüm toplam 49326 karakter]

Because of the equilibrium nature of these two ingredients, the studies that follow will simply recite “Ammonia” for most cases, regardless of whether Ammonia or Ammonium Hydroxide was reported. Absorption, Distribution, Metabolism, and Excretion Ammonia is the principle byproduct of amino acid metabolism, and the liver is indicated as the central organ of Ammonia metabolism.9 It is generated, in vivo, from the breakdown of nitrogenous substances in the gut and from the use of glutamine as a metabolic fuel in the small intestine, and is taken up by the liver where it is detoxified by conversion to urea and, to a lesser extent, glutamine.23,24 The main source of in vivo Ammonia generation occurs in the intestines, from lysis of blood-borne urea and also from protein digestion/deamination by urease-positive bacteria and microbial deaminase.25,26 A large amount of metabolically-generated Ammonia is absorbed into the blood and, via the portal vein, is detoxified by the liver.25,27,28 The normal concentration of Ammonia in the portal blood varies from 300 to 600 μM. But, in the blood leaving the liver the concentration is reduced to 20–60 μM. This confirms that the liver occupies a central position in the regulation of Ammonia levels in the organism.29,30 According to another source, the normal range for blood serum levels is of 10-40 µmol/L.31 The substrates from which Ammonia may be formed in the gut comprise derivatives of ingested nitrogenous material, epithelial and bacterial debris, and compounds secreted from the circulation to the mucosal cells and lumen (e.g., certain peptides, amino acids, and smaller diffusible substances such as urea).32 Both the gut and kidneys generate substantial amounts of Ammonia from the deamidation of glutamine.9 The glutamine-glutamate cycle in the body works in conjunction with the glucose alanine cycle to shuttle Ammonia from peripheral to visceral organs. … [kırpıldı — bölüm toplam 4901 karakter]

Because of the equilibrium nature of these two ingredients, the studies that follow will simply recite “Ammonia” for most cases, regardless of whether Ammonia or Ammonium Hydroxide was reported. Acute Toxicity Studies Acute toxicity studies (animals studies) are summarized in Table 4 (oral studies) and in Table 5 (inhalation studies). Dermal Acute dermal toxicity studies on Ammonia were not found in the published literature, nor were these data submitted. Oral Either no effects or no serious effects were reported for Ammonia in single oral exposure animal studies. However, when 0.3% Ammonia was administered to rats by gavage (33.3 mg/kg), gastric mucosal lesions were observed within 5 minutes. An acute oral LD50 of 350 mg/kg for Ammonia in rats has been reported, and the oral administration of 1 % or 3% (w/w as Ammonium Hydroxide) to rats by gavage has produced severe hemorrhagic lesions.5,42,43,44,45,46,47,48 Inhalation In acute inhalation toxicity studies involving mice, LC50s/RD50s ranging from 303 ppm to 10,150 ppm have been reported. In 10-minute exposure studies involving mice, LC50s of ≤ 10,150 ppm have been reported. In mice exposed to Ammonia (100-800 ppm) for 30 minutes, an RD50 (exposure concentration that produced a 50% reduction in respiratory rate) of 303 ppm was reported. The following effects were observed in mice that were exposed to Ammonia at a concentration of 21,400 ppm for 30 minutes: eye irritation, dyspnea, histopathological changes in the lungs (alveolar disruption and loss of septal continuity), coma, and death. Within the range of concentrations tested (3440 ppm to 12,940 ppm) in 1-h exposure studies involving mice, the following effects have been observed: hepatic lesions, congestion, and necrosis; eye irritation; dyspnea; pneumonitis and atelectasis; histopathological changes in the lung (alveolar disruption and loss of septal continuity), … [kırpıldı — bölüm toplam 15328 karakter]

Developmental/reproductive toxicity studies are summarized in Table 7. Ammonia and Diammonium Phosphate (included as a potentially similar ammonium salt) A relationship between the duration of exposure and the incidence of exencephaly (concentration-related increase) was observed in an in vitro study in which mouse embryos were cultured with Ammonia (38 to 300 µmol/l) for up to 93 h. In a developmental toxicity study involving pregnant rats exposed to Ammonia in the diet (4293 mg/kg/day; as the ammonium ion) from gestation day 1 through day 21 of lactation, body weights of offspring were reduced by 25% (males) and 16% (females). Neither reproductive nor developmental toxicity was reported in a study in which female pigs were exposed (inhalation exposure) to ~7 ppm or ~35 ppm Ammonia from 6 weeks prior to breeding until day 30 of gestation. In a reproductive and developmental toxicity study on diammonium phosphate involving rats (oral dosing), an NOAEL of 1500 mg/kg/day and an LOAEL of >1500 mg/kg/day were reported. The only histological findings relating to maternal toxicity were the inflammatory/degenerative changes in all treatment groups (diammonium phosphate at 250, 750, and 1500 mg/kg/day), which were considered likely to have been tye result of an irritant effect.3,5,48,56,85, 86,87

In Vitro Ammonia was non-genotoxic when tested at concentrations up to 25,000 ppm (with and without metabolic activation) in the following bacterial strains: Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, TA1538, and Escherichia coli strain WP2 uvr A.5,56,48  Distributed for comment only -- do not cite or quote Ammonia was non-genotoxic to E. coli strain Sd-4-73 in an in vitro assay without metabolic activation.48 In Vivo Femoral bone marrow cells were examined for polychromatic erythrocytes, and there was no evidence of genotoxicity at the doses administered. Blood samples from 22 workers who had been exposed to Ammonia (concentrations unknown) in a fertilizer factory were compared with samples obtained from 42 unexposed controls. Results (compared to controls) were as follows: increased frequency of chromosomal aberrations, sister chromatid exchanges, and mitotic index, with increasing duration of exposure. However, regarding these results, it has been noted that there are a number of limitations in this study, including gaps in the analysis, small study size, and possible confounding factors such as smoking and exposure to other chemicals.3,5,20,48,56,88 Ammonia and Ammonium Chloride (included as a potentially similar ammonium salt) An increased frequency of micronuclei (compared to controls) was observed in Swiss albino mice that received single intraperitoneal doses of Ammonia (12, 25, or 50 mg/kg). In the micronucleus test, groups of 10 (5 males, 5 females) ddY mice received single intraperitoneal (i.p.) doses of 62.5, 125, 250 and 500 mg/kg ammonium chloride or i.p. doses of 31.3, 62.5, 125, and 250 mg/kg ammonium chloride (4 injections within 24 h).5

EPA ToxValDB skin/eye data — endpoint: skin irritation: in vivo, classification: Corrosive, species: rabbit, study: skin irritation, guideline: OECD Guideline 404 (Acute Dermal Irritation / Corrosion) equivalent or similar to, year: 1977. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.

EPA ToxValDB skin/eye data — endpoint: Skin Irritation, classification: Skin Corr. 1B. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.

EPA ToxValDB skin/eye data — endpoint: Eye Irritation, classification: Category 1. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.

EPA ToxValDB skin/eye data — endpoint: Skin Sensitization, classification: Classification not possible. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.

EPA ToxValDB skin/eye data — endpoint: Eye Irritation, classification: Category 8.3A (Category 1). Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.