Amines, C10-14-tert-alkyl

Acute Toxicity: dermal

Administrative data

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: Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Amines, C10-C14-tert-alkyl

EC Number:

701-175-2

Cas Number:

68955-53-3

Molecular formula:

C10H23N to C14H31N

IUPAC Name:

Amines, C10-C14-tert-alkyl

Test animals

Species:

rat

Strain:

other: Crl:CD BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River-Kingston, Stone Ridge, New York
- Age at study initiation: approximately 55 days old (males); approximately 65 days old (females)
- Weight at study initiation: 223 to 248 g (males); 206 to 243 g (females)
- Fasting period before study: not reported
- Housing: one/cage in suspended stainless steel cages
- Diet (e.g. ad libitum): Purina certified rodent chow 5002(C)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approximately one week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 to 24 degrees C
- Humidity (%): 41 to 46%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light/ 12 hours dark


IN-LIFE DATES: From: July 21, 1992 To: August 4, 1992

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: Neutral Oil 100 N

Details on dermal exposure:

TEST SITE
- Area of exposure: entire trunk between the flank and shoulders- approximatelly 6 x 6 cm
- % coverage: not reported
- Type of wrap if used: polyethylene sheet covered with Elastoplast (Beiersdorf, Inc. Norwalk, Connecticut) and PEG (Becton-Dickinson Co. Franklin Lakes, New Jersey) elastic bandages secured in place with adhesive tape.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): After 24 hours, the backs were wiped with water-soaked paper towels.
- Time after start of exposure: after 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.0 mL/kg
- Concentration (if solution): none
- Constant volume or concentration used: yes
- For solids, paste formed: not appicable


VEHICLE Neutral Oil 100 N- contains 100% of refined paraffinic distillate
- Amount(s) applied (volume or weight with unit): 2.0 mL/kg
- Concentration (if solution): none
- Lot/batch no. (if required): 8-0419
- Purity: no data

Duration of exposure:

24 hour

Doses:

50, 200, and 400 mg/kg

No. of animals per sex per dose:

36

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs observed 0.5, 1, 2, and 4 hr after dosing and once daily for 14 days. Body weights recorded on day 0 (prior to dosing) and on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

The mortality incidences of males and females were compared across doses with a categorical data modelling procedure using SAS CATMOD (SAS Institute, Inc. SAS User's Guide: Statistics, Version 5 Edition, p 171-253. Cary, NC: SAS Institute Inc., 1985). The criterion of statistical significance was 0.05. If the results indicate a significant difference between the mortality responses for males and females, the LD50 is calculated separately by sex; otherwise the LD50 is calculated on the pooled mortality incidences at each dose.
The LD50, 95% confidence limits, and slope were calculated from the logarithm of the doses and the incidences of mortality using a SAS PROBIT procedure (SAS Institute, Inc. SAS User's Guide: Statistics, Version 5 Edition, p 171-253. Cary, NC: SAS Institute Inc., 1985) based on the method of D.J. Finney (Probit Analysis, Third Edition, London: Cambridge University Press, 1971).

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

251 mg/kg bw

95% CL:

> 190 - < 322

Mortality:

- Time of death: Males - 1 at 200 mg/kg 4 hr post-dosing (day 0); 3 at 400 mg/kg 2 hr post-dosing (day 0); 3 at 400 mg/kg 4 hr post-dosing (day 0). Females - 1 at 200 mg/kg 4 hr post-dosing (day 0); 1 at 200 mg/kg on day 1; 5 at 400 mg/kg 4 hr post-dosing (day 0). A dose-related increase in mortality was observed in the 200- and 400-m/kg dose groups.
- Number of deaths at each dose: (number of deaths/number treated)
Dose (mg/kg) 50 200 400
Males 0/6 1/6 6/6
Females 0/6 2/6 5/6

Clinical signs:

other: No mortalities and no clinical signs related to the test substance were seen in the 50- mg/kg dose group. Clinical signs indicative of neurotoxicity (tremors and/or convulsions) were observed in survivors as well as decedents in the 200- and 400-mg/kg do

Gross pathology:

Necropsy of the decedents revealed numerous skin irritation effects related to the test substance. No gross changes observed in survivors.

Other findings:

- Potential target organs: skin
- Other observations: no statistically significant sex-related differences

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Executive summary:

The dermal toxicity of the test material was evaluated in Crl:CD BR rats. The test material was dispersed in neutral oil and applied topically to the shaved intact skin of three groups of rats (6/sex/group) at 50, 200 or 400 mg/kg (2 ml/kg) body weight. The application sittes were occluded for 24 hr. After the 24 -hr exposure, the application sites were washed with tap water. No mortalities and no clinical signs related to the test substance were seen in the 50 mg/kg dose group. A dose-related increase in mortality was observed in the 200 and 400 mg/kg dose groups. Clinnical signs indicative of neurotoxicity (tremors and/or convulsions) were observed in survivors as well as decedents in the 200 and 400 mg/kg dose groups. Surviving animals recovered from the neurotoxic effects in this study. There was no apparent test substance related body weight effects in thsi study. Numerous skin irritation effects were seen in both sexes at all doses. No treatment related signs were seen at necropsy (other than skin irritaion). The overall no observed effect level (NOEL) was 50 mg/kg.

Sincec no statistically significant sex-related difference in mortality was observed, the LD50 was calculated from the combined mortality incidence data. The acute dermal LD50 in male and female rats (combined) was 251 mg/kg with 95% confidence limits of 190 and 322 mg/kg.