Carbamic acid, (2-hydroxypropyl)-, compd. with 1-amino-2-propanol (1:1)

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: gene mutation

Remarks:

Type of genotoxicity: other: gene mutation and small chromosomal deletions

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

publication

Title:

Chemical Mutagenesis Testing in Drosophila. IX. Results of 50 coded compounds tested for the National Toxicology Program

Author:

Foureman P

Year:

1994

Bibliographic source:

Env Mol Mutagen 23, 51-63

Materials and methods

Principles of method if other than guideline:

standard procedure as described in detail by Woodruff et al., Env. Mutagen. 6, 189-202, 1984 and others:
Adult Canton-S males were subjected to a 3 day feeding exposure. They were mated to Basc females using a 2 to 3 day brooding pattern for a total of three broods spanning 7 days. If the feeding SLRL test were negative, an injection exposure was performed. As in the feeding exposure, a 2 to 3 day brooding pattern for three broods was used.

GLP compliance:

not specified

Type of assay:

Drosophila SLRL assay

Test material

Test material information

Constituent 1

Reference substance name:

1-aminopropan-2-ol

EC Number:

201-162-7

EC Name:

1-aminopropan-2-ol

Cas Number:

78-96-6

IUPAC Name:

1-aminopropan-2-ol

Constituent 2

Reference substance name:

1-amino-2-propanol

IUPAC Name:

1-amino-2-propanol

Details on test material:

- Name of test material (as cited in study report): Mono-isopropanolamin
- Analytical purity: 96.4 %

Test animals

Species:

Drosophila melanogaster

Strain:

other: Canton S

Sex:

male

Administration / exposure

Route of administration:

other: oral feed; if the compound failed to induce mutations, injection exposure was used

Vehicle:

for injection: distilled water

Details on exposure:

exposure levels were chosen based on solubility, palatability, and toxicity of the chemical. In range-finding studies, an attempt was made to find a concentration resultin in approximately 30% mortality after 72 h of feeding or 24 h after injection. The maximum concentration for feeding and injection was arbitrarily set to 50.000 ppm.

Duration of treatment / exposure:

feeding study: 3 days; If the results of the feeding SLRL test were negative, a single injection exposure was performed

Frequency of treatment:

continuously in feed

Doses / concentrations

Remarks:

Doses / Concentrations:
feeding study: 24000 ppm, injection: 1900 ppm
Basis:

No. of animals per sex per dose:

no data; a minium of 5000 chromosomes were scored in each of the treated and concurrent control groups, unless the mutant frequency exceeded 1%.

Control animals:

yes, concurrent no treatment

Examinations

Evaluation criteria:

A minimum of approximately 5,000 chromosomes were scored in each of the treated and concurrent control groups, unless the mutant frequency exceeded 1%. Clusters were identified using the Poisson distribution (Owen, 1962) and were removed before analysis.

Statistics:

The statistical evaluation of a SLRL test included a comparison with the concurrent solvent control using the normal approximation to the binomial distribution, as presented by Margolin et al. (1983), as well as a comparison with the historical control as described by Mason et al. (1992). In order to be considered mutagenic, the mutant frequency in the treated sample must exceed 0.15% with a P value of less than 0.05, or the treated frequency must exceed 0.1% with a P value of less than 0.01. If the treated frequency was between 0.1% and 0.15% and the P value was between 0.1 and 0.01; or if the treated frequency was higher than 0.15%, and the P value was between 0.1 and 0.05 the assay was considered equivocal. All other assays were considered negative.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Remarks:

In range-finding studies, an attempt was made to find a concentration resultin in approximately 30% mortality after 72 h of feeding or 24 h after injection. The maximum concentration for feeding and injection was arbitrarily set to 50.000 ppm.

Vehicle controls validity:

valid

Any other information on results incl. tables

Dose (ppm)	Route	Mortality (%)	Sterility (%)	Lethals			Tests			Total lethals	Total tests	Lethals (%)
				Br1	Br2	Br3	Br1	Br2	Br3
24000	feeding	5	17	1	0	2	2658	1421	847	3	4926	0.06
0				1	0	1	2875	2748	2414	2	8037	0.02
1900	injection	14	8	2	2	2	1911	1675	1562	6	5148	0.12
0				0	2	0	1739	1493	1079	2	4311	0.05

one cluster of 3 in the injection control and one of 4 in the treated feeding experiment

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative

Executive summary:

Isopropanolamine was tested for mutagenic activity in germ cells of male Drosophila melanogaster using the sex linked recesssive lethal (SLRL) assay. After 3 days oral exposure via feed with 24000 ppm isopropanolamine followed by a 2 -3 day brooding pattern for a total of 3 broods spanning 7 days the test item was judged as non-mutagenic. This result was verified by a second experiment with injection exposure to 1900 ppm isopropanolamine. The test item was judged negative in the Drosophila SLRL assay.