Registration Dossier

Administrative data

Description of key information

Skin sensitisation of the test substance was evaluated by a weight of evidence approach.

All three studies (GPMT, Buehler, modified Buehler) revealed that the test substance is not considered to be a contact skin sensitizer.

Results of one Alarie-test showed that the test substance is also not a respiratory sensitizer.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
Modified Buehler test:
20 female animals were indiced by epidermal application of 0.4 ml (25% in water) of the test substance (3 times on 3 following weeks).
10 animals were included in the challenge control group and 10 in rechallenge control group.
The positive control dinitrochlorobenzene (DNBC) was applied to 5 animals with additional 3 animals as DNBC challenge control.
Blood samples were collected before and after the test period. After each induction, test sites were scored for dermal irritation. Following a rest period of 14 days, animals were exposed to challenge dose.
A rechallenge was performed on the test and challenge control animals 7 days after the challenge procedure. The extent and degree of skin reaction to the challenge exposure in the test animals is compared with that demonstrated by control animals which undergo sham treatment during induction and receive the challenge exposure.
GLP compliance:
yes
Remarks:
(Life Sciences Division, Springborn Laboratories Inc.)
Type of study:
Buehler test
Justification for non-LLNA method:
Study from 1991
Specific details on test material used for the study:
- Name of test material (as cited in study report): Caprolactam
- Physical state: white flakes
- Lot/batch No.: S1:600142 F from BASF Corporation Chemicals Division, New Jersey
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
Except as noted below, all animal housing and care conformed to AAALAC standards and to those published in the Guide for the Care and Use of Laboratory Animals, NIH Publication No. 86-23.

TEST ANIMALS
- Source: Harlan Sprague Dawley Inc., Indiana
- Housing: single
- Diet (e.g. ad libitum): Agway Prolab Guinea Pig formula
- Water (e.g. ad libitum): rap water
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light):12/12
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
0.4 ml of 25 % test substance in water for induction and challenge
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
0.4 ml of 25 % test substance in water for induction and challenge
No. of animals per dose:
Test group: 20
Challenge control group: 10
Rechallenge control group: 10
Positive control group: 5
DNCB Challenge control group: 3
Details on study design:
RANGE FINDING TESTS:
A repeated (3x) application preliminary irritation screen was performed to determine an appropriate concentration of the test article for induction and challenge. Four concentrations of Caprolactam were applied to the exposed skin of 4 each range-finding animals: 75%, 50%, 25% and 10% w/v Caprolactam in sterile water. Each concentration was first applied to a Webril patch (0.4 ml/patch) and the patches immediately applied to the animals. Approximately 6 hours after dosing, the dental dam and patches were removed and sites were graded for dermal irritation at 24 hours after the exposure according to the following scale:
0 - No reaction
± - Slight patchy erythema
1- Slight confluent or moderate patchy erythema
2 - Moderate erythema
3 - Severe erythema with, or without edema

Based on slight patchy erythema and desquamation, concentration of 25% was chosen for induction, challenge and rechallenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test group: a Webril patch containing 0.4 ml of 25% w/v Caprolactam in sterile water
- Control group: a Webril patch containing 0.4 ml of sterile water
- Site: left shoulder
- Frequency of applications: 3 (1 per week)
- Duration: 3 weeks
- Following each induction, test sites were scored for dermal irritation using the scale presented previously (24 and 48 hours postdose).

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- 14 day rest period
- Exposure period: 6 h
- Test group: a Webril patch containing 0.4 ml of 25% w/v Caprolactam in sterile water
- Control group: a Webril patch containing 0.4 ml of sterile water
- Site: posterior left flank
- Evaluation (hr after challenge): 24 and 48 according to the Dermal Irritation Grading System as described above


C. RECHALLENGE EXPOSURE
- No. of exposures: 1
- 7 day rest period after first challenge
- Exposure period: 6 h
- Test group: a Webril patch containing 0.4 ml of 25% w/v Caprolactam in sterile water
- Control group: a Webril patch containing 0.4 ml of sterile water
- Site: posterior left flank
- Evaluation (hr after challenge): 24 and 48 according to the Dermal Irritation Grading System as described above


Challenge controls:
10 guinea pigs for challenge control and 10 guinea pigs for Rechallenge control group.
Positive control substance(s):
yes
Remarks:
dinitrochlorobenzene (DNCB)
Positive control results:
Challenge with DNCB produced substantially stronger dermal responses, demonstrating that the test system could detect potential contact sensitizers.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25% in water
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25% in water. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25% in water
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25% in water. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
25% in water
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 25% in water. No with. + reactions: 0.0. Total no. in groups: 10.0.

Minimal dermal irritation (grades 0 to ±) was observed in both the test and negative control animals at challenge (table 1) and rechallenge (data not shown). Group mean dermal scores were also comparable between groups.

Table 1: Responding animals versus total animals in the challenge.

 

Dermal score

24h

48h

Test 25%

+/-

18/20

4/20

Control 25%

+/-

8/10

2/10

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results, the test substance is not considered a contact sensitizer in guinea pigs under the conditions of this test.
Executive summary:

A modified Buehler test was performed. 20 female animals were indiced by epidermal application of 0.4 ml (25% in water) of the test substance (3 times on 3 following weeks). 10 animals were included in the challenge control group and 10 in rechallenge control group. The positive control dinitrochlorobenzene (DNBC) was applied to 5 animals with additional 3 animals as DNBC challenge control.

Blood samples were collected before and after the test period. After each induction, test sites were scored for dermal irritation. Following a rest period of 14 days, animals were exposed to challenge dose.

A rechallenge was performed on the test and challenge control animals 7 days after the challenge procedure. The extent and degree of skin reaction to the challenge exposure in the test animals is compared with that demonstrated by control animals which undergo sham treatment during induction and receive the challenge exposure.

Based on the results, the test substance is not considered a contact sensitizer in guinea pigs under the conditions of this test.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
with GLP
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
Twenty female animals were induced by intra-dermal application to 0.1 ml (3 %) of the test substance with FCA, followed by epidermal application in the treatment group. 5 animals were included in the challenge control group.
The positive control dinitrochlorobenzene (DNBC) was applied to 5 animals with additional 3 animals as DNBC challenge control.
Blood samples were collected before and after the test period.
Following a rest period of 14 days, animals were exposed to the challenge dose.
The extent and degree of skin reaction to the challenge exposure in the test animals was compared with that demonstrated by control animals which undergo sham treatment during induction and receive the challenge exposure.
GLP compliance:
yes
Remarks:
(Life Sciences Division, Springborn Laboratories Inc.)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study report from 1991
Specific details on test material used for the study:
- Name of test material (as cited in study report): Caprolactam
- Physical state: white flakes
- Lot/batch No.: S1:600142 F from BASF Corporation Chemicals Division, New Jersey
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
Except as noted below, all animal housing and care conformed to AAALAC standards and to those published in the Guide for the Care and Use of Laboratory Animals, NIH Publication No. 86-23.
TEST ANIMALS
- Source: Harlan Sprague Dawley Inc., Indiana
- Housing: single
- Diet (e.g. ad libitum): Agway Prolab Guinea Pig formula
- Water (e.g. ad libitum): tap water
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light):12/12
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Induction: 0.1 ml of 3 % test substance in water and 0.8 ml of 75% (w/v) test substance,
Challenge: 0.4 ml of 75 % (w/v) test substance in water
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction: 0.1 ml of 3 % test substance in water and 0.8 ml of 75% (w/v) test substance,
Challenge: 0.4 ml of 75 % (w/v) test substance in water
No. of animals per dose:
Test group: 20
Challenge control group: 5
Positive control group: 5
DNBC Challenge control group: 3
Details on study design:
1st application: Induction 3 % intracutaneous
2nd application: Induction 75 % occlusive epicutaneous
3rd application: Challenge 75 % occlusive epicutaneous

RANGE FINDING TESTS:
For the topical irritation screen, 4 concentrations (10, 25, 50 and 75% w/v in water, 4 animals/conc.) of Caprolactam were applied to the clipped skin of each animal under occlusive conditions. Approximately 24 hours after dosing, patches were removed from each animal and the test sites wiped with gauze moistened with distilled water. Approximately 21 hours later, the test sites were shaved (if necessary) and three hours thereafter, the test sites were graded for irritation according to the Dermal Irritation Grading System. The grading was repeated approximately 24 hours later (48 hour scores).

For the intra-dermal irritation screen, 4 concentrations (0.1, 1.0, 3.0 and 5.0% w/v in water, 4 animals/conc.) of Caprolactam were injected intradermally (0.1 ml/injection) to each animal. Approximately 24 and 48 hours later, the test sites were graded for irritation according to the Dermal Irritation Grading System as described for topical application:
0 - No reaction
± - Slight patchy erythema
1 - Slight but confluent or moderate patchy erythema
2 - Moderate confluent erythema
3- Severe erythema with or without edema

The results indicated that a test article concentration of 3.0 % w/v would be appropriate for the intradermal induction since it was the highest dose that did not produce excessive ulceration of the test sites. A 75% w/v concentration of Caprolactam was chosen for topical induction and challenge due to the minimal response noted at 24 hours post-dose and the complete resolution of the responses by 48 hours (see chapter 7.3.1 for details).


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (1x3 intra-dermal injection on day 1 and 1x topical application for 24 h on day 8)
- Test groups: On day 1, three pairs of intra-dermal injections were made in the clipped area of the study animals:
a. 0.1 ml of FCA/sterile water for injection, (1:1 v/v)
b. 0.1 ml of test article (3.0% w/v) in sterile water for injection,
c. 0.1 ml of test article (3.0% w/v) in FCA/sterile water for injection, (1:1 v/v)
On day 8, each animal received a patch consisting of 0.8 ml of the 75% w/v Caprolactam in sterile water over the intra-dermal site for 24 h under occlusive conditions.
- Challenge Control group: On day 1, three pairs of intra-dermal injections were made in the clipped area of the study animals:
a. 0.1 ml of FCA/sterile water for injection, (1:1 v/v)
b. 0.1 ml of sterile water for injection,
c. 0.1 ml of vehicle (3.0% w/v) in FCA/sterile water for injection, (1:1 v/v)
On day 8, each animal received a patch consisting of 0.8 ml of the sterile water over the intra-dermal site for 24 h under occlusive conditions.
- Site: scapular area



B. CHALLENGE EXPOSURE
- No. of exposures: 1
- 14 day rest period
- Exposure period: 24 h
- Test groups: 0.4 ml of the 75% w/v Caprolactam in sterile water
- Control group: 0.4 ml of the sterile water
- Site: hip area
- Evaluation (hr after challenge): 24 and 48 according to the Dermal Irritation Grading System as described above


OTHER: 2 days ahead of application of the test substance and following the 48 hour scoring, a blood sample was obtained from each animal (orbital sinus) for evaluation of leukocyte and differential parameters. A second blood plasma sample was then obtained from the descending vena cava from 10 Caprolactam test animals (those showing the strongest dermal responses), the 5 Caprolactam controls and the 5 DNCB test animals for evaluation of plasma histamine.
Challenge controls:
5 guinea pigs
Positive control substance(s):
yes
Remarks:
dinitrochlorobenzene
Positive control results:
Challenge with DNCB produced substantially stronger dermal responses in all animals previously induced with the positive control demonstrating that the test system could detect potential contact sensitizers. However, there were no differences in leukocyte, differential or plasma histamine data.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.75 % in water
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.75 % in water. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.75 % in water
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.75 % in water. No with. + reactions: 0.0. Total no. in groups: 20.0.

Following challenge with the test substance, dermal responses in the test group consisted of grade ± reactions (13/20) and grade 1 reactions (7/20). Slight edema was also observed at 7/20 test sites at the 24 hours interval. By 48 hours, a grade 1 reaction was noted in 1/20 test animals (see table 1).

Dermal responses in challenge control group animals consisted of a grade 1 reaction (with slight edema) in 1/5 animals at 24 hours and of grade ± to 0 responses at all other control sites during the scoring intervals. The skin effects in the control group animals after challenge treatment are an indication of an irritation reaction to the used test concentration.

Challenge with DNCB produced substancially stronger dermal responses in all DNCB-induced animals.


No differences were observed between the challenge control and Caprolactam induced animals concerning leukocyte, differential or plasma histamine data. Evaluation of the tests regarding the skin sensitization potential is limited by using an irritant concentration for the challenge treatment. Based on the concurrent reaction in the control group animals and the fading of reactions from 24 to 48 hours, caprolactam is not considered to be a contact sensitizer under the test conditions chosen.

Table 1: Respending animals versus total animals in the challenge.

 

Dermal score

24h

48h

Test 75%

+/-

13/20

14/20

 

1

7/20

1/20

   slight edema  7/20  0/20

Control 75%

 +/-  4/5  4/5
   1  1/5  0/5
   slight edema  1/5  0/0
Interpretation of results:
GHS criteria not met
Conclusions:
No difference in the skin reactions of the test and control groups was observed after induction and challenge exposures. The test substance is therefore not considered a contact sensitizer in guinea pigs under the conditions of this test.
Executive summary:

Twenty female Hartley guinea pigs were induced by intra-dermal application to 0.1 ml (3 %) of the test substance with FCA,  followed by epidermal application in the treatment group. 5 animals were included in the challenge control group. The positive control dinitrochlorobenzene (DNBC) was applied to 5 animals with additional 3 animals as DNBC challenge control. Blood samples were collected before and after the test period. Following a rest period of 14 days, animals were exposed to the challenge dose. The extent and degree of skin reaction to the challenge exposure in the test animals was compared with that demonstrated by control animals which undergo sham treatment during induction and receive the challenge exposure.

No difference in the skin reactions of the test and control groups was observed after induction and challenge exposures. The test substance is therefore not considered a contact sensitizer in guinea pigs under the conditions of this test.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
Buehler test:
20 female animals were induced by epidermal application of 0.4 ml (75% in water) of the test substance (3 times on 3 following weeks).
5 animals were included in the challenge control group. The positive control dinitrochlorobenzene (DNBC) was applied to 5 animals with additional 3 animals as DNBC challenge control.
Blood samples were collected before and after the test period. After each induction, test sites were scored for dermal irritation.
Following a rest period of 14 days, animals were exposed to challenge dose. The extent and degree of skin reaction to the challenge exposure in the test animals was compared with that demonstrated by control animals which undergo sham treatment during induction and receive the challenge exposure.
GLP compliance:
yes
Remarks:
(Life Sciences Division, Springborn Laboratories Inc.)
Type of study:
Buehler test
Justification for non-LLNA method:
Study from 1991
Specific details on test material used for the study:
- Name of test material (as cited in study report): Caprolactam
- Physical state: white flakes
- Lot/batch No.: S1:600142 F from BASF Corporation Chemicals Division, New Jersey
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
Except as noted below, all animal housing and care conformed to AAALAC standards and to those published in the Guide for the Care and Use of Laboratory Animals, NIH Publication No. 86-23.

TEST ANIMALS
- Source: Harlan Sprague Dawley Inc., Indiana
- Housing: single
- Diet (e.g. ad libitum): Agway Prolab Guinea Pig formula
- Water (e.g. ad libitum): rap water
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light):12/12


Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
0.4 ml of 75 % test substance in water for induction and challenge
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
0.4 ml of 75 % test substance in water for induction and challenge
No. of animals per dose:
Test group: 20
Challenge control group: 5
Positive control group: 5
DNCB Challenge control group: 3
Details on study design:
RANGE FINDING TESTS:
For the topical irritation screen, 4 concentrations (10, 25, 50 and 75% w/v in water, 4 animals/conc.)) of Caprolactam were applied to the clipped skin of each animal under occlusive conditions. Approximately 24 hours after dosing, patches were removed from each animal and the test sites wiped with gauze moistened with distilled water. Approximately 21 hours later, the test sites were shaved (if necessary) and three hours thereafter, the test sites were graded for irritation according to the Dermal Irritation Grading System. The grading was repeated approximately 24 hours later (48 hour scores).
For the intra-dermal irritation screen, 4 concentrations (0.1, 1.0, 3.0 and 5.0% w/v in water) of Caprolactam were injected intradermally (0.1 ml/injection) to each animal. Approximately 24 and 48 hours later, the test sites were graded for irritation according to the Dermal Irritation Grading System as described:
0 - No reaction
± - Slight patchy erythema
1 - Slight but confluent or moderate patchy erythema
2 - Moderate confluent erythema
3- Severe erythema with or without edema

A 75% w/v concentration of Caprolactam was chosen for topical induction and challenge due to the minimal response noted at 24 hours post-dose and the complete resolution of the responses by 48 hours.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test group: a Webril patch containing 0.4 ml of 75% w/v Caprolactam in sterile water
- Control group: a Webril patch containing 0.4 ml of sterile water
- Site: left shoulder
- Frequency of applications: weekly
- Duration: 3 weeks


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- 14 day resing period
- Exposure period: 6 h
- Test group: a Webril patch containing 0.4 ml of 75% w/v Caprolactam in sterile water
- Control group: a Webril patch containing 0.4 ml of sterile water
- Site: posterior left flank
- Concentrations: 75 %
- Evaluation (hr after challenge): 24 and 48 according to the Dermal Irritation Grading System as described above


OTHER: 2 days ahead of application of the test substance and following the 48 hour scoring, a blood sample was obtained from each animal (orbital sinus) for evaluation of leukocyte and differential parameters. A second blood plasma sample was then obtained from the descending vena cava from 10 Caprolactam test animals (those showing the strongest dermal responses), the 5 Caprolactam controls and the 5 DNCB test animals for evaluation of plasma histamine.
Challenge controls:
5 guinea pigs
Positive control substance(s):
yes
Remarks:
dinitrochlorobenzene (DNCB)
Positive control results:
The positive control produced substantially stronger dermal responses in all animals, demonstrating that the test system could detect potential contact sensitizers. Although there were no apparent differences in leukocyte, differential or plasma histamine data in these animals which would correlate with the noted sensitization response to DNCB.

Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.75 % in water
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.75 % in water. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.75% in water
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.75% in water. No with. + reactions: 0.0. Total no. in groups: 20.0.

Following challenge with the test substance, dermal responses at 24 hours in the test group consisted of grade ± reactions (16/20) and grade 1 reaction (4/20). Slight edema was also observed at 7/20 test sites at this interval (see table 1).

By 48 hours, grade 1 reactions were noted in 2/20 test animals with grade ± observed in all remaining test animals (18/20). Slight edema was observed at 9/20 sites in this grading interval. Slight desquamation was reported from 1/20 animal.

Responses in the challenge control animals consisted of a grade 1 reaction (without edema) in 1/5 challenge control animals at 24 hours with grade ± responses (without edema) noted at all other control sites during the scoring intervals. No differences were observed between the control and the test substance induced animals concerning leukocyte, differential or plasma histamine data.

Table 1: Responding animals versus total animals in the challenge.

 

Dermal score

24h

48h

Test 75%

+/-

16/20

18/20

 

1

4/20

2/20

 

Slight edema

7/20

9/20

Control 75%

+/-

4/5

5/5

 

1

1/5

0/5

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results where no difference in the skin reactions of the test and control groups was observed after induction and challenge exposures, the test substance is not considered a contact sensitizer in guinea pigs under the conditions of this test.
Executive summary:

20 female Hartley guiney pigs were induced  by epidermal application of 0.4 ml (75% in water) of the test substance (3 times on 3 following weeks). 5 animals were included in the challenge control group. The positive control dinitrochlorobenzene (DNBC) was applied to 5 animals with additional 3 animals as DNBC challenge control. Blood samples were collected before and after the test period. After each induction, test sites were scored for dermal irritation. Following a rest period of 14 days, animals were exposed to challenge dose. The extent and degree of skin reaction to the challenge exposure in the test animals was compared with that demonstrated by control animals which undergo sham treatment during induction and receive the challenge exposure.

Based on the results where no difference in the skin reactions of the test and control groups was observed after induction and challenge exposures, the test substance is not considered a contact sensitizer in guinea pigs under the conditions of this test.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin Sensitization

The test substance was tested similar to OECD guidelines in a guinea pig maximization test (challenge: 75% CAP in water), in a Buehler test (challenge: 75% CAP in water) and in a modified Buehler test (challenge: 25% CAP in water) and was considered to be not sensitizing (Industrial Health Foundation, 1991).

In the maximization test, twenty female animals were induced by intra-dermal application of 0.1 ml (3 %) of the test substance with FCA, followed by an epidermal application. Following a 14 day rest period, challenge was performed with an epidermal application of the test substance (75%).

Slight to moderate patchy erythema and slight edema were observed 24h after challenge in the test group and in the negative control group (induction with water challenge with the test substance).

Dermal responses regressed at the second reading (48h), although still observable.

The skin effects in the control group animals after challenge treatment are an indication of an irritation reaction to the applied test concentration and therefore the test substance is not considered to be a contact sensitizer under the test conditions chosen.

In the Buehler test, twenty female animals were induced by 3 epidermal applications to 0.4 ml (75% in water) of the test substance (on 3 consecutive weeks).

Again comparable reactions between animals previously induced with the test substance and challenge control guinea pigs were observed (slight to moderate patchy erythema and slight edema). An apparent increase in the occurrence of slight edema in the induced animals following challenge was addressed to the primary irritation of the test substance and not to a sensitization reaction. Summarized, the test substance is not considered a contact sensitizer in guinea pigs under the conditions of this test.

A second, modified Buehler test was performed with a reduced test substance concentration (25%) in order to minimize the interference of dermal irritation with the sensitization read out. In a range finding assay 25% of the test substance was identified as the highest dose that produced only transient, minimal cumulative primary irritation following repeated (3x) applications over a one week period. With this test concentration only minimal dermal irritation (grades 0 to ±) was observed in both the test and negative control animals at challenge and rechallenge. Group mean dermal scores were also comparable, and thus, the test substance was not considered to be a contact sensitizer under the test conditions chosen. 

 

In a skin-painting test (with 50% of the test substance) and following intracutaneous application (with 1% of the test substance), no sensitization reactions were observed with challenge concentrations of 50% of the test substance (BASF XII/315, 1966).

 

Apart from reliable studies, there are few human studies. The test substance (5 %) produced no signs of irritation or indication of sensitization reactions when applied to the forearms of five volunteers (Goldblatt et al., 1954). In two of four cases with eczema on the legs after wearing nylon stockings a positive patch test (test substance 5 %) was reported (Jansson, 1959). Occupational contact dermatitis in a textile worker handling nylon fibers with an 18-month history of itchy, erythematous scaly eczema on the neck, chest and limbs was confirmed by patch testing (test substance 5 % aq) (Aguirre et al., 1995). Considering the rarely reported cases in human and negative results in reliable animal studies (with GLP), the test substance does not require classification as skin sensitizer.

 


Migrated from Short description of key information:
Not sensitizing in guinea pig maximization test and Buehler test.

Respiratory sensitisation

Link to relevant study records
Reference
Endpoint:
respiratory sensitisation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
Sensitization reactions to the test substance aerosols were observed by exposing groups of 4 guinea pigs for 30 min/day for 5 consecutive days to 3 aerosol concentrations (3, 10 and 30 mg/m³ which corresponds to 0.003, 0.01 and 0.03 mg/l).
Each animal was placed in a whole body plethysmograph attached to a primary chamber. This device can detect pressure changes induced by the breathing activity of the test animals.
On days 19, 26, 33 and 40, all three groups of animals were challenged with CO2, then given a 30 minute challenge of 30 mg/m³ test substance and another CO2 challenge 45 minutes later. After the last challenge, lungs were removed from all animals and grossly examined.
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material (as cited in study report): E-Caprolactam
- Physical state: white flakes
- Lot/batch No.: D344A441 from BASF Corp. Chemical Division, Freeport, Texas
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hazleton Labs Inc., Denver, PA
- Weight at study initiation: 381-455 g
- Diet (e.g. ad libitum): Ralston Purina Guinea Pig Chow
- Water (e.g. ad libitum): Tap water
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12
Route of induction exposure:
inhalation
Route of challenge exposure:
inhalation
Vehicle:
water
Concentration:
3, 10 and 30 mg/m³ which corresponds to 0.003, 0.01 and 0.03 mg/L
No. of animals per dose:
4
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 5
- Exposure period: 30 min
- Each animal was placed in a whole body plethysmograph attached to a primary chamber. A sensitive differential pressure transducer (Gaeltec 8T-2) was attached to each whole body plethysmograph. With each breath, a pressure change (AP) was created in the whole body plethysmograph and detected by the transducer.
- A 15% solution of caprolactam was prepared in distilled water. The solution was placed in a 30 ml syringe with a 20g needle attached. The syringe was fitted into a Harvard (Model 975) compact syringe pump which was set to deliver at 0.7 ml/minute. It was connected to the aerosol generator. The aerosol generator was pressurized at 15 psi with dry air. An additional 10 L/min of dry air was introduced at the side port of the Y tube at the entrance of the primary chamber. Thus, dry particles of caprolactam were produced for inhalation by the animals. The various concentrations of caprolactam were obtained by varying the exhaust airflow of the primary chamber from 20 L/min to 70 L/min.


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: On days 19, 26, 33 and 40
- Exposure period: 30 min
- All three groups of animals were challenged with CO2, then given a 30 minute challenge of 30 mg/m³ caprolactam and another CO2 challenge 45 minutes later.



FIRST 5 DAYS OF CONSECUTIVE EXPOSURES:
no significant respiratory responses to the test substance. Only one cough was noted during the entire series of experiments. Therefore, there was no evidence of any kind of acute irritating or bronchoconstricting properties.


CHALLENGE DAYS:
no immediate reaction, no evidence of an immediate hypersensitivity reaction and no abnormal respiratory responses to the test substance. Ventilatory response to the CO2 challenges was normal.

Interpretation of results:
study cannot be used for classification
Conclusions:
Under the conditions of this experiment, the test substance can not induce respiratory sensitization reaction even at the highest concentration (30 mg/m3) tested.
Executive summary:

Sensitization reactions to the test substance aerosols were observed by exposing groups of 4 guinea pigs for 30 min/day for 5 consecutive days to 3 aerosol concentrations (3, 10 and 30 mg/m³ which corresponds to 0.003, 0.01 and 0.03 mg/l). Each animal was placed in a whole body plethysmograph attached to a primary chamber. This device can detect pressure changes induced by the breathing activity of the test animals.

On days 19, 26, 33 and 40, all three groups of animals were challenged with CO2, then given a 30 minute challenge of 30 mg/m³ test substance and another CO2 challenge 45 minutes later. After the last challenge, lungs were removed from all animals and grossly examined. Under the conditions of this experiment, the test substance can not induce respiratory sensitization reaction even at the highest concentration (30 mg/m3) tested.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Respiratory sensitization:

In an Alarie-test with induction exposures on 5 subsequent days (max. aerosol concentration of 30 mg/l), no respiratory responses were detected, neither during the induction phase nor following a single challenge exposure of 30 mg/l (IHF, 1990).

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 or respiratory sensitization under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No 2018/1480.