Hydroxylamine

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

CAS No. 10039-54-0:

Some informations related to reproductive organs can be derived from the data of a repeated dose toxicity study, during which Wistar rats (10 animals/sex/dose group) had been exposed to hydroxylammonium sulfate (purity > 99%) via drinking water for over 3 months at concentrations of 10, 50, and 250 ppm according to dose levels of about 0.9, 4, and 21 mg/kg bw/d . Organ weight determinations of testes at all dose levels as well as macro- and microscopic evaluations of the testes at the highest dose level (250 ppm) had been performed for the male sex, whereas with females only macro- and microscopic evaluations had been performed for the uterus and the ovary at the highest dose level (250 ppm). At the end of the study for neither of these parameters any substance related changes could be detected. It is concluded from this study that hydroxylammonium sulfate does not interfere with reproductive organ weights and morphological integrity at dose levels of up to and including 250 ppm according to a daily intake of approximately 21 mg/kg bw (NOAEL). The NOAEL for systemic adverse effects of this study was 0.9 mg/kg bw/d for both sexes based on findings of hemolytic anemia with methemoglobinemia and changes in organ weight as well as histopathological changes in spleen and liver at higher dosages (BASF AG 1992, Val. 2).

During two studies, both with limited validity, focussing on the investigation of hydroxylammonium sulfate for its tumour preventive properties in both a mouse and a rat mammary gland tumour model also the ductile development of mammary glands and the morphology of mammary glands (mouse and rat) and the morphology of the ovaries (mouse) was monitored for prolonged drinking water application of high doses of hydroxylammonium sulfate (10 mM hydroxylammonium sulfate in drinking water according to an intake of approximately 100 mg/kg bw/d for mice and 67 mg/kg bw for rats) in hydroxylammonium sulfate only treated animals. The results of these two studies show that in rodents the female sex higher dosages of hydroxylammonium sulfate may interfere with the estrus cycle and with the functional state and morphology of reproductive organs (ovaries). As evidenced by morphological signs of either atrophy or hypertrophy and secretion also the functional state and the morphological development and integrity of the mammary gland may be affected. With respect to these findings a LOAEL of 67 mg/kg bw/d can be inferred from these studies (Evarts and Brown 1977; Evarts et al. 1979; both Val. 3).

CAS No. 5470-11-1:

No valid data available concerning reproductive toxicity.

CAS No. 7803-49-8:

No valid data available concerning reproductive toxicity.

Short description of key information:
CAS No. 10039-54-0:
- 3 months, oral, rat: NOAEL P >= 21 mg/kg bw (BASF AG 1989, Val. 2)

Effects on developmental toxicity

Description of key information

CAS No. 10039-54-0:
- Oral, rat, gestation day 6-15: maternal toxicity: NOAEL  = 3 mg/kg bw; embryo-/fetotoxicity: NOAEL >= 20 mg/kg bw (OECD 414), (BASF AG 1994, Val. 1)

Additional information

CAS No. 10039-54-0:

An OECD 414 guideline study is available for the assessment of the developmental toxicity potential. In this study hydroxylammonium sulfate was investigated for its prenatal toxicity in Wistar rats by the oral (gavage) route of administration. Groups of 22 - 24 pregnant rats had been treated with hydroxylammonium sulfate at dosages of 1, 3, 10, and 20 mg/kg bw on day 6 through day 15 post coitum. The test substance (purity > 98.4%) had been administered as an aqueous solution and at a standard dose volume of 5 ml/kg bw. The control group, consisting of 20 dams, was dosed with the vehicle (Milli-Q-water) only. Food consumption and body weights of the animals were recorded regularly throughout the study period. The state of health of the animals was checked each day. At sacrifice on day 20 post coitum dams were assessed by gross pathology (including weight determinations of the spleen), and numbers of corpora lutea and numbers and distributions of implantation sites were recorded. Foetuses were sexed, weighed and further investigated for any external, soft tissue and/or skeletal findings. In the dams an enlargement of the spleens and a dose related statistically significant increase in absolute and relative spleen weights was revealed at dosages of 10 and 20 mg/kg bw/d. No substance-related effects on dams were reported for the lower dose groups. There were no substance-related differences between the groups in conception rate, the mean number of corpora lutea and implantation sites or in the values calculated for the pre- and the postimplantation losses, the number of resorptions and of viable foetuses. Mean fetal body weight of the dosed groups did not differ from that of the control. Examination of foetuses did not reveal any signs for substance related abnormalities. From this study a NOAEL for maternal toxicity of 3 mg/kg bw/d and a NOAEL for embryo-/fetotoxicity of >= 20 mg/kg bw/d can be derived (BASF AG 1994, Val. 1).

CAS No. 5470-11-1:

In a publication which is not assessable due to methodological deficiencies (De Sesso, 1990; Val.3) severe maternal toxicity was observed. Seven pregnant female rabbits were injected subcutaneously with 50 mg/kg and embryos were collected at five or eight hours after treatment. All 21 embryos collected from 3 does at 5 h post-treatment were alive with uteri appearing cyanotic. All embryos exhibited dilations of the anterior and posterior cardial veins; 10/21 had petechial hemorrhages in the cranial region and 7/21 red fluid in the pericardial cavity. At 8 h, all 16 embryos from 2 does showed no active heartbeat and were considered nonviable.

In a further study with an unusual application route (intracoelomic injection) which permitted hydroxylamine to bypass the maternal system and allowed direct exposure of the developing embryo (De Sesso, 1990; Val. 3) HA caused the deaths of 31/32 embryos that were exposed to 100 μg HA or more. The lone surviving fetus was growth retarded and exhibited osseous defects of the skull and sternum. At lower doses of HA, the percentage of embryonic deaths decreased, although it remained significantly higher than in controls. These results demonstrate that embryonic exposure to HA is developmentally toxic, with the primary manifestation being embryonic lethality.

CAS No. 7803-49-8:

No valid data available concerning developmental toxicity/teratogenicity.

Justification for classification or non-classification

Due to the lack of toxicity on fertility and development in definite studies there is no need for classification according to reproductive toxicity.

According to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, Annex VI the classification is:

not classified