Amines, C10-14-tert-alkyl

Endpoint summary

Description of key information

Substance is considered a sensitizer

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report which meets basic scientific principles

Qualifier:

according to guideline

Guideline:

other: Modified Buehler (Ritz and Buehler, 1980)

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

This substance has been demonstrated to be a non-sensitizer in a guideline compliant studies, therefore potency data as generated in an LLNA is not needed.

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Kingston, Stone Ridge, New York
- Age at study initiation: not reported
- Weight at study initiation: 426 - 632 g
- Housing: 1/cage in wire mesh cages
- Diet (e.g. ad libitum): ad libitum, Purina guinea pig chow
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 70 to 75 degrees C
- Humidity (%): 48-66%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark


IN-LIFE DATES: From: August 20, 1984 To: September 26, 1984

Route:

epicutaneous, occlusive

Vehicle:

other: ethanol

Concentration / amount:

0.4 mL of a 3.0% w/v ethanol solution induction
0.4 mL of a 1.0% w/v in acetone challenge

Route:

epicutaneous, occlusive

Vehicle:

other: ethanol

Concentration / amount:

0.4 mL of a 3.0% w/v ethanol solution induction
0.4 mL of a 1.0% w/v in acetone challenge

No. of animals per dose:

30

Details on study design:

RANGE FINDING TESTS: Range finding skin irritation tests were conducted on 16 naive guinea pigs to determine the slightly irritating concentration (SIC) to be used for induction and the highest non-irritating concentration (HNIC) to be used for challenge. Eight concentrations: 50%, 25%, 12.5%, 6.0%, 3.0%, 1.0%, 0.5% and 0.25% w/v test material in absolute ethanol and the same concentrations in acetone were applied to the skin sites. The application sites were changed among the guinea pigs for each of the above concentrations to minimize any site-to-site variation in irritation response.

The range-finding primary skin irritation tests results on 32 naïve guinea pigs were 3% in absolute ethanol for induction and 1% in acetone for challenge.
RESULTS OF TEST -
Sensitization reaction:
Induction Incidence Irritation/Sensitization
24 hr 48 hr
3% (w/v) in ethanol 0/10 (0.2) 0/10 (0.1)

Challenge
1% in acetone 15/19 (1.4) 10/19 (0.7)

Note: the value in parenthesis represents the mean dermal score (i.e., the intensity of the irritation response) - Clinical signs: At a challenge concentration of 1% test material in acetone, 15 of the 19 guinea pigs induced with test material responded with erythema of grade 1 or greater while none of the non-induced guinea pigs responsed with erythema of grade 1 or greater.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10
- Exposure period: three 6 hr periods per week for 3.5 consecutive weeks
- Test groups: 19 guinea pigs
- Control group: yes; receiving SHAM treatment during induction
- Site: back of the guinea pigs
- Frequency of applications: 10 applications over a 3.5 week period
- Duration: 6-hr
- Concentrations: 3.0%


B. CHALLENGE EXPOSURE- after a two-week rest period
- No. of exposures: 1
- Day(s) of challenge: 48 hours
- Exposure period: approximately 24 hours after the challenge application, the backs of the guinea pigs were depliated with NEET(R) lotion hair remover. The depilatory was liberally applied to the clipped application sites and allowed to remain on the animlas for approximately 20 minutes. The animals were then rinsed with lukewarm running tap water, blotted dry, and then returned to their cages.
- Test groups: 19 treated guinea pigs from the induction group and a group of 10 naive guinea pigs
- Control group: yes, from induction group
- Site: back of the guinea pigs
- Concentrations: 1.0% w/v test material
- Evaluation (hr after challenge):


OTHER: No rechallenge

Challenge controls:

Non-induced challenge controls

Positive control substance(s):

no

Positive control results:

Not applicable

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1.0% w/v in acetone

No. with + reactions:

15

Total no. in group:

19

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1.0% w/v in acetone. No with. + reactions: 15.0. Total no. in groups: 19.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1.0% w/v in acetone

No. with + reactions:

10

Total no. in group:

19

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1.0% w/v in acetone. No with. + reactions: 10.0. Total no. in groups: 19.0.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

1.0% w/v in acetone

No. with + reactions:

0

Total no. in group:

19

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 1.0% w/v in acetone. No with. + reactions: 0.0. Total no. in groups: 19.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

1.0% w/v in acetone

No. with + reactions:

0

Total no. in group:

19

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1.0% w/v in acetone. No with. + reactions: 0.0. Total no. in groups: 19.0.

Interpretation of results:

sensitising

Conclusions:

Under these test conditions, the test material produced DCH in guinea pigs induced with the test material.

Executive summary:

The delayed contact hypersensitivity *DCH potential of the test material was tested in young adult outbred Hartley guinea pigs (GP). Ten induction doses (0.4 ml) of 3.0% (W/V) test material in absolute ethanol were applied to the backs of an induction group of 9 male and 10 female GP for three 6 -hr periods per week for 3.5 consecutive weeks. Two weeks after the last induction treatment, the 19 GP in the induction group and a group of 10 naive control GP were each "challenged" with 0.4 ml of a 1.0% (W/V) solution of test material in acetone. Erythema reactions were scored at 24 and 48 hours after the challenge exposure. At a challenge concentration of 1.0% (W/V) test material in acetone, 15 of 19 test material induced GP responded with an erythema reaction of grade 1 or greater while no grade 1 or greater reactions were observed in the 10 non-induced controls. Under these test conditions, the test material produced DCH in guinea pigs induced with the test material.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The test material in acetone/ethanol produces contact sensitization, however its ability to sensitize appears to be vehicle/carrier-dependent. The test material did not produce contact sensitisation with mineral oil as vehicle. Skin sensitization was determined in a modified Buehler method in guinea pigs. The test material in acetone/ethanol produces contact sensitization (15/19 pigs with grade 1 or greater reactions). The test material (67% Primene in oil) was not sensitizing in guinea pigs when mineral oil was used as solvent vehicle.

Migrated from Short description of key information:
Skin sensitisation- sensitizing in guinea pigs in a modified Buehler assay.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The test material in acetone/ethanol produces contact sensitization (15/19 pigs with grade 1 or greater reactions).