Dibutylamine

Endpoint summary

Description of key information

The test substance showed no skin sensitizing potential.

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

Study period:

July 1 - August 10 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4100 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

The study was conducted before the protocol for the LLNA was in place (OECD adopted in 2002).

Species:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Davidson's Mill Farm, S. Brunswick, NJ
- Weight at study initiation: 332-448g
- Housing: 5 per suspended stainless steel cage
- Diet: Purina Guinea pig Pellets ad libitum
- Water: tap water ad libitum
- Acclimation period: 24 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.9-22.2°C (66-72°F)

Route:

epicutaneous, occlusive

Vehicle:

other: Ethanol 80%

Concentration / amount:

6% in Ethanol 80%

Route:

epicutaneous, occlusive

Vehicle:

other: Ethanol 80%

Concentration / amount:

6% in Ethanol 80%

No. of animals per dose:

10 males for the treated group
10 males for the negative control group
10 males for the positve control group

Details on study design:

RANGE FINDING TESTS: Determination of the non-irritating dose
Two guinea pigs were clipped on the thoracolombar region. 0.5ml of the test material as an 8% or 4 % solution in 80% Etahnol and as an 2 % or 1% solution in 60% Ethanol was applied. Each site was covered with a 2.5cm2 diameter gauze patch. After 6 hours of exposure, the patches were removed.
Readings were realised 24 hours later.
The highest non-irritating dose for induction was established to be 6% in 80 % Ethanol.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10
- Exposure period: 6 hours/exposure
- Site: dorsal thoracolombar area
- Frequency of applications: once every 48 hours
- Concentrations: 6%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 days after the last induction exposure
- Exposure period: 6 hours
- Site: dorsal thoracolombar area
- Concentrations: 6 %
- Evaluation (hr after challenge): at 24 and 48 hours

Challenge controls:

none

Positive control substance(s):

yes

Remarks:

Dinitrochlorobenzene 0.08% in 95% Ethanol

Positive control results:

During induction period with DNCB, all guinea pigs exhibited erythema. Severity ranged from 0.5 (very faint, non-confluent) to 2.0 (moderate).
During challenge period with DNCB, six test sites were erythemateous 24 hours after challenge. Four sites were clear. At 48 hours , 8 sites had erythema and only 2 were clear. erythema scores ranged from 0.5 (very faint, non-confluent) to 3.0 (strong).

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

0.08%

No. with + reactions:

6

Total no. in group:

10

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

0.08%

No. with + reactions:

8

Total no. in group:

10

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

6%

No. with + reactions:

4

Total no. in group:

10

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

6%

No. with + reactions:

0

Total no. in group:

10

Reading:

1st reading

Hours after challenge:

24

Group:

other: negative control 1

Dose level:

0%

No. with + reactions:

1

Total no. in group:

5

Reading:

2nd reading

Hours after challenge:

48

Group:

other: negative control 1

Dose level:

0%

No. with + reactions:

1

Total no. in group:

5

Reading:

1st reading

Hours after challenge:

24

Group:

other: negative control 2

Dose level:

0%

No. with + reactions:

2

Total no. in group:

5

Reading:

2nd reading

Hours after challenge:

48

Group:

other: negative control 2

Dose level:

0%

No. with + reactions:

2

Total no. in group:

5

Induction:

Faint non-confluent erythema which was sporadic and transient was observed throughout the induction period. Eschar, scabbing, and or skin discoloration were noted between the 5th and the 7th application. this did not re-occur when the test material was applied to an adjacent site.

Challenge:

Five sites exhibited wery faint non-confluent erythema 24 hours after challenge. the 5 remaining sites were clear. By 48 hours all challenged sites were clear. There was no evidence of oedema at either time interval.

in naive control guineapigs, one test site had very faint non-confluent erythema 24 and 48 hours after dosing. The 4 remaining previously naive sites were clear.

Individual results (challenge):

Sensitization scores - Test substance	Challenge score
Guinea pig N°	24h	48h	Induced sensitization
2715	0,5	0	1+
2716	0	0	0
2717	0	0	0
2718	0	0	0
2719	0,5	0	1+
2720	0,5	0	1+
2721	0,5	0	1+
2722	0	0	0
2723	0	0	0
2724	0,5	0	1+
Naive control
2725	0	0	0
2726	0	0	0
2727	0,5	0,5	1+
2728	0	0	0
2729	0	0	0

Sensitization scores - control	Challenge score
Guinea pig N°	24h	48h	Induced sensitization
2715	0	0	0
2716	0	0,5	0
2717	1	1	1+
2718	2	1	2+
2719	2	1	2+
2720	3	2	3+
2721	0	0,5	0
2722	1	0,5	1+
2723	0,5	0,5	1+
2724	0	0	0
Naive control
2725	0,5	0,5	1+
2726	0	0	0
2727	0	0	0
2728	0,5	0,5	1+
2729	0	0	0

Under these experimental conditions, the test substance is negative in the Buehler test.

Interpretation of results:

GHS criteria not met

Conclusions:

A Bühler Test according to EPA OPPTS 870.2600 (Skin Sensitisation) was performed in male guinea pigs (Hartley). Under these experimental conditions, the test substance is negative in the Buehler test.

Executive summary:

A Bühler Test according to EPA OPPTS 870.2600 (Skin Sensitisation) was performed in male guinea pigs (Hartley). The guinea pigs were treated with 6 % of the test substance in 80% Ethanol epicutaneous (occlusive) for 6 hours. 10 males for the treated group, 10 males for the negative control group and 10 males for the positve control group (Dinitrochlorobenzene 0.08% in 95% Ethanol) were used.

RESULTS OF THE POSITIVE CONTROL:

During induction period with DNCB, all guinea pigs exhibited erythema. Severity ranged from 0.5 (very faint, non-confluent) to 2.0 (moderate). During challenge period with DNCB, six test sites were erythemateous 24 hours after challenge. Four sites were clear. At 48  hours , 8 sites had erythema and only 2 were clear. erythema scores ranged from 0.5 (very faint, non-confluent) to 3.0 (strong).

RANGE FINDING TESTS: Determination of the non-irritating dose

Two guinea pigs were clipped on the thoracolombar region. 0.5ml of the test material as an 8% or 4 % solution in 80% Etahnol and as an 2 % or 1% solution in 60% Ethanol was applied. Each site was covered with a 2.5cm2 diameter gauze patch. After 6 hours of exposure,  the patches were removed. Readings were realised 24 hours later. The highest non-irritating dose for induction was established to be 6% in 80 % Ethanol.

                           

MAIN STUDY

A. INDUCTION EXPOSURE

Guniea pigs were exposed 10fold to 6% of the test substance for 6 hours/exposure at the dorsal thoracolombar area site. The frequency of applications was once every 48 hours.

Faint non-confluent erythema which was sporadic and transient was observed throughout the induction period. Eschar, scabbing, and or skin discoloration were noted between the 5th and the 7th application. this did not re-occur when the test material was applied to an adjacent site.

                                  

B. CHALLENGE EXPOSURE

Guniea pigs were exposed 1fold to 6% of the test substance for 6 hours at the dorsal thoracolombar area site. The evaluation was performed 24 and 48 hours after the challenge.

Five sites exhibited wery faint non-confluent erythema 24 hours after challenge. the 5 remaining sites were clear. By 48 hours all challenged sites were clear. There was no evidence of oedema at either time interval.

in naive control guineapigs, one test site had very faint non-confluent erythema 24 and 48 hours after dosing. The 4 remaining previously naive sites were clear.

Under these experimental conditions, the test substance is negative in the Buehler test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

A Buehler test according to EPA OPPTS 870.2600 was carried out in 10 guinea pigs per group (1988; K2). The test compound (6% solution) was applied to the skin for a 6 h treatment period 10 times once each 48 h. This induction series was followed after 2 weeks by a 6 h challenge on the depilated flanks of each animal (test substance concentration: 6%). Five sites exhibited very faint non-confluent erythema 24 hours after challenge. The 5 remaining sites were clear. By 48 hours all challenged sites were clear. There was no evidence of edema at either time interval. In negative control animals, one test site had very faint non-confluent erythema 24 and 48 hours after dosing. The DCNB-inducted and challenged groups showed 60% and 80% positive response at 24-hour and 48-hour evaluations, respectively.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. Results show that the test substance is not considered to be classified for skin sensitization under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No 2018/1480.