Hydroxylamine

Endpoint summary

Description of key information

For hydroxylamine (free base) no data is available. However, valid studies of the corresponding salts "hydroxylamine sulfate" and "hydroxylamine chloride" are available:
CAS No. 10039-54-0:
Oral
Rat:
LD50 = 642 mg/kg bw (BASF 1969, Val. 2)
LD50 ca. 3160 mg/kg bw (BASF 1975, Val. 3) 
Cat:
LD50 > 50 and < 200 mg/kg bw for females and > 200 mg/kg bw for males (BASF 1981, Val. 2)
Inhalation
Rat, IHT: 8 h: No mortality occurred at room temperature (BASF 1969, Val. 3) 
Rat, IHT: 7 h: No mortality occurred at room temperature (BASF 1980, Val. 3) 
Rat, IHT: 8 h: No mortality occurred at room temperature (BASF 1975, Val. 3) 
Dermal
- Rat: 
LD50 > 500 mg/kg bw (Derelanko 1987, Val. 1; occlusive test conditions)
- Rabbit: 
LD50 > 1000 mg/kg bw (Derelanko 1987, Val. 1; semiocclusive test conditions)
LD50 > 100 and < 500 mg/kg bw (Derelanko 1987, Val. 1; occlusive test conditions)
LD50 > 400 mg/kg bw (BASF 1980, Val. 2)
LD50 > 1500 and < 2000 mg/kg bw (Allied Corp. 1983, Val.1; semiocclusive test conditions).
CAS No. 5470-11-1:
Oral
Rat:
LD50 ca. 600 mg/kg bw (BASF AG 1975, Val. 2)
Mouse:
LD50 ca. 408 mg/kg bw in males and 419 mg/kg bw in females (Riemann 1950, Val. 2)
Inhalation
Rat, IHT: 8 h: No mortality occurred at room temperature (BASF 1975, Val. 3) 
Dermal
No data available.

Additional information

For hydroxylamine (free base) no data is available. However, valid studies of the corresponding salts "hydroxylamine sulfate" and "hydroxylamine chloride" are available:

CAS No. 10039-54-0:

Oral

There are valid data available for the assessment of the acute oral toxicity of hydroxylammonium sulfate. Five male and five female Sprague-Dawley rats were treated each with 200, 400, 500, 640, 800, 1000, 1250, 1600 mg/kg bw, administered as oral application of 2 % and 4 % aqueous solutions of chemically pure test material under standardized conditions; the test method was comparable to OECD guideline 401. The animals were observed for 14 d, necropsy was performed even with the survivors. The LD50 was 642 mg/kg bw for male and female rats.Clinical signs observed included dyspnoea, trembling, convulsions, tremors and lateral position. At necropsy, blue-violet discoloration and distension of the spleen were detected (BASF, 1969).

An oral LD50 of approximately 200 mg/kg bw was detected for female cats in a study on the methaemoglobin formation properties of hydroxylammonium sulfate (purity 99.5 %). Toxic effects following oral application of single doses of 50 mg/kg bw to 1 male and 1 female cat and single doses of 200 mg/kg bw to 3 male and 3 female cats were assessed (aqueous solution dispensed by gavage).The application of 50 mg/kg was survived by both cats which demonstrated methaemoglobin concentrations of 12.1 % resp. 21.6 % at the 4-hours observation time. After application of 200 mg/kg bw hydroxylammonium sulfate 0/3 male and 2/3 female cats died; in this group between 10.0 % and 41.9 % methaemoglobin was detected 4 hours after substance application. Clinical signs in the 50 mg/kg bw group included increased salivation, cyanosis and vomiting; in the 200 mg/kg bw group repeated vomiting, increased salivation, apathia, cyanosis, mydriasis and lateral position were observed. Based on these effects, a LD50 > 50 and < 200 mg/kg bw for females and > 200 mg/kg bw for malesfor cats was derived. Deaths occurred 2 days after application, the surviving animals recovered within 9 days. Necropsy of the cats that died revealed weak heart muscles, acute passive hyperemia, discolored liver and lungs (BASF, 1981).

Another study with limited reliability provided a LD50 of ca. 3160 mg/kg bw in rats (BASF 1975, Val. 3).

Inhalation

There is no valid information available on studies performed in order to detect the inhalation LC50 ofhydroxylammonium sulfate nor is there any information on methaemoglobin formation after inhalation of the substance. No studies using hydroxylammonium sulfate vapours are available. Three inhalation risk tests with rats demonstrate that inhalation of saturated vapours (saturated at 20°C) did not cause severe toxic effects in this species. However, due to the physico-chemical properties of the substance (solid at room temperature and salt character) the vapour pressure ofhydroxylammonium sulfate is assumed to be very low, the concentration of hydroxylammonium sulfate after saturation in air must also be very low. Hence, it is questionable whether the method used in the two reported inhalation studies led to significant, toxicologically relevant concentrations of hydroxylammonium sulfate. Saturated vapours of chemically pure hydroxylammonium sulfatewere produced by conducting air through a 5 cm layer of the substance at 20°C. These saturated vapours were inhaled by 12 rats for a period of 8 hours. None of the rats died and no clinical signs were observed. Autopsy revealed no relevant findings (BASF 1969, Val. 3).

In a second study 12/12 rats survived a 7-hour exposure period to saturated vapours ofhydroxylammonium sulfate (purity 99.5 %). Saturated vapours were produced by conducting 200 l air per hour through a 5 cm layer of the substance at 20°C (method according to Smyth et al., 1962). The resulting vapours were let into one-animal inhalation chambers for a 7-hour exposure periods and animals were observed following exposure after 3 min, 10 min, 30 min, 1 hour, 3 hours, 7 hours and thereafter daily. All animals survived within a 14-days observation period. No clinical signs were observed. At necropsy, no changes were detected (BASF 1980, Val. 3).

Another standardized inhalation hazard test was conducted to assessthe acute inhalation toxicity of saturated vapours of the tested material. saturated vapours. All animals survived, no clinical signs were observed, and no abnormalities were found in the organs. However, the substance tested was not equivalent to submission substance identity (BASF 1975, Val. 3).

Dermal

There are valid data available for the assessment of the acute dermal toxicity of hydroxylammonium sulfate.The acute dermal toxicity of hydroxylammonium sulfateis different for rats and rabbits. Furthermore, the findings were different depending on the kind of bandage used in order to occlude the substance applied.

A test with rats resulted in a dermal LD50 higher than 500 mg/kg bw. Female rats were exposed for 24 hours to a single application of hydroxylammonium sulfate (purity >98 %) moistened with water. The test material was held in contact with the skin by wrapping the torso of the rat with a polyethylene bandage. One group of animals received test material via a sc injection (as a 1 % aqueous solution). Ten animals per group were exposed to doses of 500, 100 and 10 mg/kg. Subcutaneous injection of 10 mg/kg of the substance was utilized as a rough indicator of complete dermal absorption of the test material. All animals were observed closely at least twice each day for gross signs of toxicity, blood samples were collected from all animals, methaemoglobin determination was performed on day 2. Erythrocyte, leukocyte, platelet, and reticulocyte counts, as well as determinations of total haemoglobin, hematocrit, mean corpuscular haemoglobin concentration, were determined from days 4 and 14 blood samples. No mortality occurred within this test, skin irritation of moderate incidence, and to a lesser extent necrosis and sloughing, were evident. A large percentage of the rats exposed became pale following exposure (all dose levels). This effect was evident within 24 hours and persisted to approximately 6 days, cyanosis was not observed. Other gross signs of toxicity included staining of the nares, mouth, and fore paws with brown material, yellow staining of the anogenital area, and lacrimation. Blood methaemoglobin levels determined 48 hours following initial exposure were statistically elevated over control values in all exposed groups with the greatest increase occurring in the topical 500 mg/kg group (4.0 %) and in the 10 mg/kg sc injected group (6.3 %). Heinz bodies were not observed in circulating erythrocytes. Principal findings at necropsy included a high incidence of enlarged and darkened spleens regardless of the dose level or route of exposure. Gross effects on the liver were minimal to absent (Derelanko et al. 1987).

A dermal LD50 between 100 mg/kg bw and 500 mg/kg bw was detected for rabbits in a study comparing occlusive and semi-occlusive dermal exposure.Hydroxylammonium sulfate (purity >98 %) proved strikingly more toxic when administered under plastic than under gauze despite the fact that both methods included occlusion. Female Albino rabbits were exposed for 24 hours to a single topical application of test material moistened with water. The test material was covered with either a porous gauze patch or a plastic cover. Both the gauze and the plastic covers were held in place with surgical tape. One group of animals received test material via a sc injection (as a 1 % aqueous solution). Ten animals per group were exposed to doses of 500, 100, 10 and 1 mg/kg under plastic cover and doses of 1000, 500 and 100 mg/kg using gauze. Plastic covering was not used at the 1000 mg/kg level since earlier findings indicated such an exposure would be 100% lethal to the rabbit. Subcutaneous injection of 10 mg/kg of the substance was utilized as a rough indicator of complete dermal absorption of the test material. All animals were observed closely at least twice each day for gross signs of toxicity, blood samples were collected from all animals, methaemoglobin determination was performed on day 2. Erythrocyte, leukocyte, platelet, and reticulocyte counts, as well as determinations of total haemoglobin, hematocrit, mean corpuscular haemoglobin concentration, were determined from days 4 and 14 blood samples. Animals surviving for 14 days were necropsied. After occlusive skin contact with 100 mg/kghydroxylammonium sulfate 2/10 rabbits died demonstrating 18.7% methaemoglobin, in surviving animals 80 % Heinz bodies in erythrocytes were detected 4 days after exposure. After semi-occlusive skin contact with 100 mg/kg bw hydroxylammonium sulfate no deaths were noted (methaemoglobin 1.9%). After occlusive skin contact with 500 mg/kg bw 9/10 rabbits died demonstrating 60.8 % methaemoglobin concentration and formation of Heinz bodies in all animals (no quantitative data). Therefore, the LD50 in rabbits is >100 and < 500 mg/kg bw. After semi-occlusive skin contact with 500 mg/kghydroxylammonium sulfateno animals died (methaemoglobin 1.9%). Even in the 10 mg/kg bw group with occlusive exposure (none of the animals died, no methaemoglobin formation), Heinz bodies were detected in one animal 4 days after exposure. In addition, erythrocytes and reticulocyte counts were significantly decreased and increased, respectively. In contrary, within the semi-occlusive exposure groups even 1000 mg/kg bw was survived by all animals (percentage of methaemoglobin 6.2% and formation of Heinz bodies in three animals). Here, the LD50 was > 1000 mg/kg bw. The reference group with sc injection of 10 mg/kg (no mortality) revealed 5.1% methaemoglobin, and Heinz bodies were found in erythrocytes of all animals (4 days after treatment, no quantitative data). However, it is to be mentioned that there were some methodological insufficiencies concerning methaemoglobin determination on rabbits in this study (Derelanko et al., 1987).

Another test employing rabbits demonstrates again that semi-occlusive skin exposure is much less toxic. In a limit-test with rabbits the skin of 5 male and 5 female rabbits was exposed occlusively to a dose of 400 mg/kg bw hydroxylammonium sulfate (purity 99.5%) using a 50% aqueous substance solution (exposure period 24 hours). None of the rabbits died within an 8-days observation period, neither clinical signs nor local effects were detected, necropsy revealed no changes (BASF, 1980).

A dermal LD50 higher than 1500 mg/kg bw but less than 2000 mg/kg bw resulted forhydroxylammonium sulfate(no data on purity) in a further study with rabbits: Male and female rabbits from 4 test groups were treated with single applications ofhydroxylammonium sulfateat doses of 2000 mg/kg bw (6 males and 4 females), 1500 mg/kg bw (5 males and 5 females), 1000 mg/kg bw (5 males) and 500 mg/kg bw (5 males and 5 females) and observed for 14 days. Control rabbits were treated with water (5 males and 5 females). The test material was placed on gauze strip and then applied to the hairfree skin of the back. Seven of 10 rabbits died or were sacrificed in extremis at the high dose level after 3 days, all remaining rabbits survived. An acute hemorrhagic dermatitis was present in each of the 7 rabbits that died. Necropsy examination of the tissues revealed severe hemorrhagic necrosis of the skin characterized by massive subepithelial and dermal lesions which often extended from just beneath the epithelium to the cutaneous muscle layer, blood appeared brown. The skin lesions of the surviving animals were characterized by hemorrhage, edema, bulla formation, vascular congestion, and massive heterophil infiltrates. Changes in other tissues were not definitive of compound induced toxicity. It appeared, however, that the deaths may have been related to circulatory collapse (shock) brought on by neurogenic pain reflexes associated with the skin lesion. Lesions in the liver and kidneys supported this contention. Few compound associated changes were present in survivors. The skin contained residual but healing changes. The spleens of 3/3 high and 4/10 mid dose terminated rabbits contained increased amounts of hemosiderin pigment. Red cell damage was detected, other tissue alterations were judged to have been unrelated tohydroxylammonium sulfatetreatment (Allied Corporation, 1983).

 

CAS No. 5470-11-1:

Oral

There are valid data available for the assessment of the acute oral toxicity of hydroxylammonium chloride. Five male and five female Sprague-Dawley rats were treated each with 681, 464 and 316 mg/kg bw, administered asoral application of 6, 6 and 3 % aqueous solutions of chemically pure test material (purity 99%) under standardized conditions; the test method was comparable to OECD guideline 401. The animals were observed for 14 d, necropsy was performed even with the survivors. The LD50 was ca. 600 mg/kg bw for male and female rats.Clinical signs observed included a staggering walk, abdominal position, accelerated breath, cyanosis, severe convulsions, dyspnea, asphyxia seizure, exsiccosis and apathy. At necropsy, acute dilatation of the heart especially of the right prechamber and acute hyperemia was ssen in animals that died during the study; in the animals that were sacrificed after the observation period of 7 days an acute congestion of blood in the spleen was seen and the organ seemed to be swollen (BASF, 1975).

In a second study, the oral LD50 was determined in mice.10 animals per sex per dose were treated each with 200, 300, 400, 500 and 600 mg/kg bw, administered asoral application of 0.5 to 2 % aqueous solutions the test material (no data on purity given) under standardized conditions. The animals were observed for 14 d, necropsy was performed even with the survivors. The LD50 was ca. 408 mg/kg bw for male mice and ca. 419 mg/kg bw for female mice. All the dead mice contained methemoglobin. The mice that had received higher doses were dead after a few minutes, and all the other mice died within 24 hours, except one animal that died between 48 and 72 hours after administration of the test material (Riemann, 1950).

Inhalation

There is no valid information available on studies performed in order to detect the inhalative LC50 ofhydroxylammonium chloride. No studies usinghydroxylammonium chloridevapours are available. An inhalation risk test with rats demonstrates that inhalation of saturated vapours (saturated at 20°C) did not cause severe toxic effects in this species. However, due to the physico-chemical properties of the substance (solid at room temperature and salt character) the vapour pressure of hydroxylammonium chlorides assumed to be very low, the concentration of hydroxylammonium chloride after saturation in air must also be very low. Hence, it is questionable whether the method used in the two reported inhalation studies led to significant, toxicologically relevant concentrations o fhydroxylammonium chloride. Saturated vapours of chemically pure hydroxylammonium chloride were produced by conducting air through a 5 cm layer of the substance at 20°C. These saturated vapours were inhaled by 3 rats per experiment for a period of 8 hours. None of the rats died and no clinical signs were observed. Autopsy revealed no relevant findings (BASF 1975, Val. 3).

Dermal

No data available.

CAS No. 7803-49-8:

Oral

No data available.

Inhalation

No data available.

Dermal

No data available.

Justification for classification or non-classification

For the classification of hydroylamine the same justification as of hydroxylamin sulfate was used. This is warranted because the relative amounts of hydroxylamine in a ≤55% aqueous solution and in hydroxylamine sulfate crystals are comparable.

Oral:

The available data for hydroxylammonium sulfate indicate a potential for acute oral toxicity. An oral LD50 of 642 mg/kg bw was provided for rats. Therefore, hydroxylammonium sulfate has to be classified as harmful after single oral ingestion (Xn, R22) according to EU requirements and as Category 4 oral acute toxicant according to GHS requirements in this endpoint.

According to an oral acute toxicity study with cats the LD50 was found to be > 200 mg/kg bw. Methaemoglobin was detected but not primarily associated with mortality. Thus, the rat study was considered to be the most relevant study.

Dermal:

The available data for hydroxylammonium sulfate also indicate a potential for acute dermal toxicity. A dermal LD50 of > 500 mg/kg bw was provided for rats under occlusive conditions and a dermal LD50 > 1000 and < 2000 mg/kg bw was provided for rabbits under semiocclusive test conditions. Therefore, hydroxylammonium sulfate has to be classified as harmful after single dermal application (Xn, R21) according to EU requirements and as Category 4 dermal acute toxicant according to GHS requirements in this endpoint.

Inhalation:

An unsuitable test system (Val. 3) was used for assessing the inhalation toxicity of hydroxylammonium sulfate in several studies. An assessment was not possible, since the result of the inhalation hazard test is depending on the vapour pressure of the test substance (being very low for the tested substance). Nevertheless, the result supports the assumption that the tested material is of low inhalation toxicity.