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

Endpoint summary

Description of key information

The acute oral LD50 of carbamic acid, (2-hydroxypropyl)-, compound with 1-amino-2-propanol (1:1) is considered to be > 2000 mg/kg bw, based on studies with the immediate cleavage product 1-amino-2-propanol.
The acute dermal LD50 of carbamic acid, (2-hydroxypropyl)-, compound with 1-amino-2-propanol (1:1) is considered to be > 2000 mg/kg bw, based on studies with the substance in ethylene glycol.
No reliable data are available for acute inhalation toxicity. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: group entry

Principles of method if other than guideline:

old methods for acute oral toxicity testing

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Route of administration:

oral: unspecified

Dose descriptor:

LD50

Effect level:

1 715 mg/kg bw

Remarks on result:

other: reduced body temperature, diarrhoea, drowsiness

Dose descriptor:

LD50

Effect level:

4 260 mg/kg bw

Dose descriptor:

LD50

Effect level:

2 813 mg/kg bw

Remarks on result:

other: aqueous solutions of 2, 20, and 30% were administered; clinical symptoms: agitation, staggering gait, dispnoea, convulsions; macroscopic signs: none

Sex:

male

Dose descriptor:

LD50

Effect level:

2 098 mg/kg bw

Remarks on result:

other: groups of 6 rats were given 500 to 3500 mg/kg bw of the test substance; all rats were lethargic and had diarrhea and rough hair coats; no treatment related effects were observed upon pathological examination at the end of the 2 week observation period.

Executive summary:

Various early acute oral toxicity studies not performed under GLP in summary show an LD50 of > 2000 mg/kg bw for 1-amino-2-propanol in rats. Clinical signs were reported as e.g. diarrhea, rough hair coats and lethargic behaviour.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

(1987)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: RCCHan:WIST
- Source: Harlan GmbH, 5960 AD Horst, Netherlands
- Age at study initiation: approximately 9-13 weeks
- Diet and water: ad libitum
- Acclimation period: at least 5 days

Type of coverage:

other: semiocclusive, but predominantly covered with air-tight plaster

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TREATMENT
The liquid test substance was applied pure.
Treatment area: 30 cm²
TEST SITE
One day before the start of the treatment the back and flanks of the rats were shorn (approximately 10% of the body surface area). For each dose and animal the required amount of the pure liquid test substance was calculated on the base of the body weight at time of dosing. This amount was weighed and applied as uniformly and thinly as possible to the test area, covered with a gauze-layer (6.0 cm x 5.0 cm = 30.0 cm²) of a "Cutiplast steril" coated with air-tight "Leukoflex". The gauze strip was placed on the rat's back and secured with a "Lomir biomedical Inc rat jacket", which was connected with a safety pin to the stretch tape to ensure that the animals could not ingest the test substance.

REMOVAL OF TEST SUBSTANCE
After approximately 24 hours the dressings were removed and the area was rinsed with tepid water using soap and gently patting the area dry.

Duration of exposure:

24 hours

Doses:

limit dose of 2000 mg/kg bw ; according to 18.8 to 20 mg/cm² for male rats and 15.8 to 16.8 mg/cm² for female rats.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: at least 14 days
- Frequency of observations: once daily
- Frequency of weight determination: once weekly
- Necropsy of survivors performed: yes

Statistics:

none; limit dose test

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: no mortalities, clinical signs, toxicological effects on weight development and gross pathological findings

Mortality:

No mortalities occured.

Clinical signs:

other: none

Gross pathology:

The necropsies performed at the end of the study revealed no particular findings.

Interpretation of results:

not classified

Remarks:

Migrated information

Executive summary:

Carbamic acid, (2-hydroxypropyl)-, compound with 1-amino-2-propanol (1:1) in ethylene glycol was tested in an acute dermal toxicity study on rats performed according to OECD TG 402. For the purpose of a limit test 2000 mg/kg bw of the test item were applied to the skin of 5 male and 5 female rats for 24 hours. The test substance was tolerated by the animals without mortalities, clinical signs, toxicological effects on weight development and gross pathological findings. The resulting LD50 was determined with > 2000 mg/kg bw for both sexes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

A detailed justification for read-across and classification is attached to IUCLID chapter 13 (Tegethoff, 2013b).

It was shown in a hydrolysis study performed according to OECD TG 111 that carbamic acid, (2-hydroxypropyl) -, compound with 1-amino-2-propanol (1:1) is extremely unstable in acidic aqueous media and completely disintegrates into1-amino-2-propanolunder formation of CO₂within less than 5 minutes (see IUCLID section 5.1.2). Such a rapid disintegration can also be expected in the acidic environment of the stomach of laboratory animals after oral administration and of the stomach of humans in the unlikely case of accidentally oral ingestion. Thus, according to Annex VIII and XI, column 2 of REACH Regulation (EC) 1907/2006 repeated dose toxicity studies do not need to be conducted if a substance undergoes immediate disintegration and there are sufficient data on the cleavage products. The immediate cleavage product of carbamic acid, (2-hydroxypropyl) -, compound with 1-amino-2-propanol (1:1) after oral uptake is1-amino-2-propanolunder formation ofcarbon dioxide. With regard to human health effects CO₂can be considered as of minor importance (see section 7.0 of IUCLID data set). The major and relevant cleavage product1-amino-2-propanolis toxicologically well investigated, shows a comprehensive toxicological data base (see sections 7.2 to 7.8 of IUCLID data set) and has been assessed in authority based peer review processes, either for establishment of an occupational exposure level (www. baua. de) or in the ICCA/HPV progamme. Therefore, in line with Annex XI of Regulation (EC) No 1907/2006 and taking into account animal welfare considerations, no studies with oral application were performed for the product itself but read across via1-amino-2-propanolwas chosen for the registration of carbamic acid, (2-hydroxypropyl) -, compound with 1-amino-2-propanol (1:1) for all endpoints with potential oral administration (acute oral toxicity, repeated dose toxicity and reproductive toxicity). All other relevant toxicological studies have been performed with the stabilized trade product carbamic acid, (2-hydroxypropyl) -, compound with 1-amino-2-propanol (1:1) in ethylene glycol itself.

Oral route

As described above it was shown that under acidic environmental conditions carbamic acid, (2-hydroxypropyl)-, compound with 1-amino-2-propanol (1:1) immediately disintegrates into1-amino-2-propanol and carbon dioxide. Such a rapid disintegration can be expected also in the acidic environment of the stomach of laboratory animals after oral administration and of the stomach of humans in the unlikely case of accidentally oral ingestion. Thus, for evaluation of the acute oral toxicity of carbamic acid, (2-hydroxypropyl)-, compound with 1-amino-2-propanol (1:1) read-across of data for 1-amino-2-propanol was considered appropriate.

Various early acute oral toxicity studies not performed under GLP in summary show an LD50 of > 2000 mg/kg bw for 1-amino-2-propanol in rats (Burkatskaya, 1986; Smyth, 1951; Oettel and Zeller, 1965). Thus, the acute oral toxicity of carbamic acid, (2-hydroxypropyl)-, compound with 1-amino-2-propanol (1:1) is also considered with an LD50 of > 2000 mg/kg bw.

 

Inhalation route

Acute inhalation toxicity studies are not available for carbamic acid, (2-hydroxypropyl)-, compound with 1-amino-2-propanol (1:1).

 

Dermal route

Carbamic acid, (2-hydroxypropyl)-, compound with 1-amino-2-propanol (1:1) in ethylene glycol was tested in an acute dermal toxicity study on rats performed according to OECD TG 402 (Gillissen, 2012). For the purpose of a limit test 2000 mg/kg bw of the test item were applied to the skin of 5 male and 5 female rats for 24 hours. The test substance was tolerated by the animals without mortalities, clinical signs, toxicological effects on weight development and gross pathological findings. The resulting LD50 was determined with > 2000 mg/kg bw for both sexes.

Justification for selection of acute toxicity – oral endpoint
group entry

Justification for selection of acute toxicity – dermal endpoint
only one study available

Justification for classification or non-classification

A detailed justification for read-across and classification is attached to IUCLID chapter 13 (Tegethoff, 2013b).

No classification is required for acute oral and dermal toxicity based on the study results with the substance (dermal) and via read-across of the immediate cleavage product (oral). No data are available for acute inhalation toxicity.