Di(morpholin-4-yl) disulphide

Endpoint summary

Description of key information

4, 4'-dithiodimorpholine is a strong skin sensitizer in a Buehler's assay.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Remarks:

n vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Buehler's method with modifications on duration of exposition (24h, not 6h), number of treated animals (10, not 20)

GLP compliance:

not specified

Type of study:

other: Buehler's method with modifications

Justification for non-LLNA method:

An old study on guinea pigs was performed before REACH regulation. No new study on animals was performed after REACH regulation.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

not specified

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Brreding Laboratories, Inc. Mass).
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 350-420g
- Housing: in individual cages
- Diet (e.g. ad libitum): a pellet diet
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 70 +/- 2°C
- Humidity (%): 45% +/-
- Air changes (per hr): 10 /hr
- Photoperiod (hrs dark / hrs light): 12/12

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

Induction: 5%
Challenge: 0.1, 0.5 and 2%

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

Induction: 5%
Challenge: 0.1, 0.5 and 2%

No. of animals per dose:

10 animals/dose

Details on study design:

RANGE FINDING TESTS:
-Method = 2 guinea pigs were used to study the skin irritation potential for each compound, preparations of 0.5, 5, 5 and 10% being used to determine the threshold irritation concentration (TIC). 24h before testing, the hair on the flank was shaved. About 0.1 g of each compound was applied to gauze pads (6 layers) of 1.5 cm² dimension. Dermicel was wrapped around the bodies of the animals. Self-adhering foam pads were then applied over the choth tape and secured to the animals' flanks. 24h after application, the test materials were removed. Readings were performed at 1, 24 and 48h after removal of the test substance.
-Result = 5 and 10% concentrations of DTDM produced irritant reactions. The reaction intensity of the 5% preparation, however, was much weaker than of the 10% preparation. The 5% concentration of DTDM resulted in at least a minimal amount of erythema.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1
- Exposure period: 24hr
- Test groups: 0.1g
- Control group: petrolatum
- Site: hair of the nuchal region
- Frequency of applications: 3
- Duration: 2 weeks
- Concentrations: 5% in petrolatum

B. CHALLENGE EXPOSURE
- No. of exposures:
- Day(s) of challenge:
- Exposure period: 24hr
- Test groups: 0.1g
- Control group: pure petrolatum
- Site: left flank of the animals
- Concentrations: 0.1 , 0.5 , 2% in petrolatum
- Evaluation (hr after challenge): 1, 24, 48h and 7 days

Challenge controls:

no data

Positive control substance(s):

no

Positive control results:

no data

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

2%

No. with + reactions:

10

Total no. in group:

10

Clinical observations:

4 with erythema, and 6 with erythema + swelling

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 2%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: 4 with erythema, and 6 with erythema + swelling.

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.5%

No. with + reactions:

8

Total no. in group:

10

Clinical observations:

8 with erythema only

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5% . No with. + reactions: 8.0. Total no. in groups: 10.0. Clinical observations: 8 with erythema only.

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.1%

No. with + reactions:

1

Total no. in group:

10

Clinical observations:

1 with erythema

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.1%. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: 1 with erythema.

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

0.1, 0.5 and 2%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.1, 0.5 and 2%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

1st reading

Hours after challenge:

48

Group:

positive control

No. with + reactions:

10

Total no. in group:

10

Remarks on result:

other: not in the study report

Table : Results of reaction to challenge

Compounds	No. of animals	Concentration of challenge and frequency of sensitization
		2 %		0.5 %		0.1 %		pet
		+	++	+	++	+	++ *
DTDM	10	4	6	8	0	1	0	0
Reading made 48h challenge (24h after removal of the compounds tested). * Criteria for grading reactions : + = definite erythema, ++ = erythema and swelling

Interpretation of results:

Category 1A (indication of significant skin sensitising potential) based on GHS criteria

Conclusions:

When a 2 % concentration of DTDM was used for the challenge, 100% of the animals reacted to DTDM. With 0.5% concentration, there were 80%.

Executive summary:

In a modified Buehler's test, group of 10 rats were exposed to 4, 4'-dithiodimorpholine at 5% in petrolatum during the induction period and were challenged with concentrations of 0.1, 0.5 or 2% in petrolatum. Sensitizing reactions were observed in 1, 8 and 10 animals, respectively.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

In a modified Buehler's test (Wang and Suskind, 1988), group of 10 rats were exposed to 4, 4'-dithiodimorpholine at 5% in petrolatum during the induction period and were challenged with concentrations of 0.1, 0.5 or 2% in petrolatum. Sensitizing reactions were observed in 1, 8 and 10 animals, respectively.

The conclusion is the that DTDM is a skin sensitizer.

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Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data, DTDM should be classified as skin sensitizer according to the Regulation EC n°1272/2008 : Skin Sens. 1A (H317: May cause an allergic skin reaction.)

Justification: In the Buhler test, guinea pigs were induced with 5% of DTDM, and 80% or 100% showed skin reaction. The subcategory A should be selected as written in the criteria of CLP Guidance ">60% responding at > 0.2% to < 20% topical induction dose".