Diethyl sulphate, compound with 2-(heptadec-8-enyl)-4,5-dihydro-1H-imidazole-1-ethanol (1:1)

Endpoint summary

Description of key information

Information from studies on skin sensitisation reveal skin sentsitising properties. Therefore, the substance is classified as a skin irritant, Skin Irrit. 2.

The substance was examined for eye irrittaing and eye damaging properties in a study according to OECD 492. The results do not allow a decision on C&L. For precautionary reasons the self-clasification is as Eye Damage. 1.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation / corrosion, other

Remarks:

Information from study on acute dermal toxicity and skin sensitisation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Principles of method if other than guideline:

The information gathered by the studies on acute dermal toxicity and skin sensitisation reveal skin irritating properties.

GLP compliance:

yes (incl. QA statement)

Test system:

other: Information from studies on acute dermal toxicity and skin sensitisation

Species:

rat

Strain:

Wistar

Type of coverage:

occlusive

Preparation of test site:

clipped

Duration of treatment / exposure:

24 hours

Observation period:

After Test ltem application, individual animals were frequently observed approximately at 30 minutes 1, 2, 3, 4, 5 and 6 hours post Test ltem application at day O (day of dosing) subsequently all animals were observed twice a day during the 14-day observation period, after dosing.

Number of animals:

10

Details on study design:

Approximately 24 h prior to treatment, the fur of dorsal area of the trunk (approximately 10 % body surface area) of rats was clipped by using clipper.
The Test ltem, dispensed under sterile conditions in sterilized glassware, was applied uniformly over clipped dorsal intact area of rat's trunk skin. Individual rat was applied the starting dose of 2000 mg/kg bw with a volume of Test ltem, calculated based on the latest body weight and Test ltem density (1.0124 g/ml) measured at the test facility.
Test ltem as such was held completely in contact with the skin with a porous gauze dressing (greater than 10% of body surface area of rat) and non-irritating tape throughout a 24-hour exposure period. lt was ensured that the animals cannot ingest the Test ltem and rats were not immobilised. At the end of the exposure period, residual Test ltem was removed by using distilled water.

Irritation / corrosion parameter:

other: Information from studies on skin sensitisation

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Remarks:

10 animals (5 male, 5 female): 4 males and 4 females: score 2,0 1 male and 1 female: score 2,67

Time point:

24/48/72 h

Score:

2.13

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

mean

Remarks:

10 animals (5 male, 5 female): 2 males and 2 females: score 2,0 3 males and 3 females: score 2,67

Time point:

24/48/72 h

Score:

2.4

Max. score:

4

Reversibility:

not specified

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

In an acute dermal toxicity study a single dose level of 2000 mg/kg of Diethyl sulphate, compound with 2-(heptadec-8-enyl)-4,5-dihydro-1H-imidazole-1-ethanol (1:1) was administered to Wistar rats (key study, see chapter 7.2.3 acute dermal toxicity). No signs of systemic toxicity were observed, indicating primarily a low dermal toxicity (the LD50 value of the test item is more than 2000 mg/kg body weight). But well defined erythema and slight oedema were observed in all the animals. At 48 & 72 hours observation the animals showed slight to well defined erythema, two animals showed moderate to severe erythema. Moderate oedema was also observed in six animals.
Information from this studies on acute dermal toxicity and skin sensitisation reveal skin irritating and skin sensitising properties. Therefore, the substance is classified as a skin irritant, Category 2.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2018-05-31 to 2018-06-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 492 (Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage)

Version / remarks:

2017-10-09

Qualifier:

according to guideline

Guideline:

other: 4.2.2 DB-ALM Protocol n° 190: SkinEthicTM HCE Eye Irritation Test Liquid (EITL)

Version / remarks:

2017-06-07

GLP compliance:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:
R-127 / batch no. 180131
- Expiration date of the lot/batch:
2019-01-31

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
Dry and dark at ambient temperature (10 – 30 °C)
- Stability under test conditions:
stable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: none

Species:

human

Strain:

other: RhCE

Details on test animals or tissues and environmental conditions:

Test system: Reconstructed Human Corneal Epithelium, small, age day 5 (area: 0.5 cm2)
Source:
EPISKIN SNC
4, rue Alexander Fleming
69366 - Lyon Cedex 7
FRANCE

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

Application Substance Duration
Test substance 10 ± 1 µl 0.01M PBS pH = 7.4 and 30 ± 2 µl test item 30 ± 2 min
Negative contro 30 ± 2 µl 0.01M PBS pH = 7.4 30 ± 2 min
Positive control 10 ± 1 µl 0.01M PBS pH = 7.4 and 30 ± 2 µl methyl acetate 30 ± 2 min

Duration of treatment / exposure:

Duration was 30 ± 2 min

Duration of post- treatment incubation (in vitro):

37 ± 2 oC, 5 ± 1 % CO2, ≥ 90% humidity for 3 hours ± 15 minutes

Number of animals or in vitro replicates:

2

Irritation parameter:

other: OD mean value, mean viability %

Run / experiment:

T1- (final), 30 min exposure

Value:

26.4

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

not determinable because of methodological limitations

Irritation parameter:

other: OD mean value, mean viability %

Run / experiment:

T-2 (final) 30 min exposure

Value:

19.1

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

not determinable because of methodological limitations

Irritation parameter:

other: OD mean value, mean viability %

Run / experiment:

Mean viablity both runs

Value:

22.8

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

not determinable because of methodological limitations

Interpretation of results:

study cannot be used for classification

Conclusions:

Based on the SkinEthicTM HCE EIT (for the liquid’s protocol) Validated Reference Method (VRM) and associated with UN GHS classification system, the test item- Diethyl sulphate, compound with 2-(heptadec-8-enyl)-4,5-dihydro-1H-imidazole-1-ethanol (1:1), Lot No: 170825 is considered: No prediction can be made.

Executive summary:

The substance Diethyl sulphate, compound with 2-(heptadec-8-enyl)-4,5-dihydro-1H-imidazole-1-ethanol (1:1) was examined for eye irrittaing and eye damaging properties in a study according to OECD 492.

The results do not allow a decision on C&L.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Justification for classification or non-classification

Information from studies on acute dermal toxicity and on skin sensitisation reveal skin irritating and skin sensitising properties. Therefore, the substance is classified as a skin irritant, Skin Irrit. 2.

The substance was examined for eye irrittaing and eye damaging properties in a study according to OECD 492. The results do not allow a decision on C&L. For precautionary reasons the self-clasification is as Eye Irrit. 2.