Hydroxylammonium chloride

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vivo

Description of key information

Available data is sufficient to conclude that hydroxylamine hydrochloride can cause heritable genetic damage.

Link to relevant study records

Reference

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: abstracted from the summary published in the well-known publication, contributing to assessment

Qualifier:

no guideline followed

GLP compliance:

not specified

Type of assay:

chromosome aberration assay

Species:

other: locusts

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

male locusts

Route of administration:

other: abdominal injection

Vehicle:

N/A

Details on exposure:

0.05 ml hydroxylamine hydrochloride as a 0.1 M solution (equivalent to 350 µg) for 36hr

Duration of treatment / exposure:

36 hr

Frequency of treatment:

once

Remarks:

Doses / Concentrations:
0.05 ml hydroxylamine hydrochloride as a 0.1 M solution (equivalent to 350 µg)
Basis:
nominal conc.

Control animals:

yes

Sex:

male

Genotoxicity:

positive

Toxicity:

not specified

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

caused chromosome aberrations (breaks, fragmentation, bridge formation) in the spermatocytes

Conclusions:

Interpretation of results (migrated information): positive
It is concluded that hydroxylamine hydrochloride caused chromosome aberrations (breaks, fragmentation, bridge formation) in the spermatocytes based on the results given in this report.

Executive summary:

A single abdominal injection into male locusts of 0.05 ml hydroxylamine hydrochloride as a 0.1 M solution (equivalent to 350µg) caused chromosome aberrations (breaks, fragmentation, bridge formation) in the spermatocytes 36 hours later, effects which were not observed in the controls.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (positive)

Additional information

Additional information from genetic toxicity in vivo:

All available studies covered the four endpoints (i.e. gene mutation test in bacteria, in vitro chromosome aberration test, gene mutation in mammalian cells and in vivo cytogenetic assay).

Gene mutation test in bacteria (Ames test):

In this study (Springer-verlag, 1994), Hydroxylamine hydrochloride did not induce point mutations in a Salmonella/microsome test in the strains TA 1535，TA 1536，TA 1537，TA 1538，TA 98 and TA 100 at a dose of 1000 and 5000 µg/plate, either with or without metabolic activation. Herbert S. Rosenkranz, 1979 gave the consistent conclusion.

However, G. M. Paronikyan, 1975 indicated that hydroxylammonium chloride caused positive mutagenic activity with Eschevichia coti P-678. And Scher, S.; Wecher, R.A, 1982 suggested the positive results with exposed PPL-1 cells. In contrast, these agents are inactive in the Salmonella/microsome test.

Gene mutation in mammalian cell:

William J. Caspary, et al 1988 demonstrated that Hydroxylamine HCI induced mutagenic response in the mouse lymphoma cell mutagenesis assay. However, J.W.Harbell et al., 1987 suggested that HA caused negative mutation with and without metabolic activation under the conditions with and without metabolic activation (s-9).

Chromosome aberration in vitro:

Three reports were given to evaluate the gene mutation. G. Speit, C. Wick, and M. Wolf, 1980 indicated that HA produces only a slight increase in the number of SCEs and, after chronic treatment, prevents cell growth at concentrations above 5 × 10-4M. In another study (PRAMILA GUPTA and T. SHARMA, 1981), HA induced a very high frequency of damage in the secondary constriction regions of the chromosome pairs 1, X and Y2, and the frequency was slightly lower than this in the centromeres of 1, 2 and X chromosomes. J.W.Harbell et al.,1987 gave the contrary results that there is the lack of mutagenic action by HA but not the clastogenic or SEC inducing action of Hydroxylamine HCI.

In vivo chromosome aberration:

In vivo study was reported by Springer-verlag, 1994. A single abdominal injection into male locusts of 0.05 ml hydroxylamine hydrochloride as a 0.1 M solution (equivalent to 350µg) caused chromosome aberrations (breaks, fragmentation, bridge formation) in the spermatocytes 36 hours later, effects which were not observed in the controls.

Based on the total weight of evidence available, there are inconsistent results showed from in vitro data(i.e. positive or negative effects). However, in vivo data should be given more weight than that conducted in vitro. Thus, it is concluded that hydroxylamine hydrochloride can cause heritable genetic damage.

Justification for selection of genetic toxicity endpoint
Available data in vivo should be given more weight as its high relevance and reliability.

Justification for classification or non-classification

It is concluded that hydroxylamine hydrochloride can cause the positive mutagenic effects. Thus, test substance can be classified as category 2 for the mutagenicity according to CLP (EC No. 1272/2008).