Quaternary ammonium compounds, di-C8-10-alkyldimethyl, chlorides

Endpoint summary

Description of key information

There are no studies avalilable for the assessment of skin sensitisation potential of the substance. However, the substance is corrosive and so this endpoint can be waived.

There are two skin sensitisation studies available for a structurally similar substance and these have been provided for completeness.In an amended guinea pig maximisation test to evaluate the sensitisation potential of the substance male and female mice (ten animals/sex) were exposed (occlusive) topically to the substance at 0.2% w/v in water during first application followed by 7 topical (occlusive) applications at 5% w/v in water every 48 hours. Following a resting period of 12 days a challenge application was administered topically for 48 hours employing 0.2% w/v in water at 0.5 mL a site away from the site of initial induction. The skin site was monitored for any signs of irritation at 6, 24 and 48 hours post-application. A skin biopsy was taken from those animals in which irritation was observed at 6 hours following the challenge application. Macroscopic and histological evaluations were conducted on these tissues. No other animals exibited signs of irritation for the remainder of the study.Macroscopic and histological evaluations were conducted on these tissues as well. The findings indiacte that the substance is not a skin sensitiser or is a weak sensitiser as reported by the study facilitator. In the second study a Beuhler assay was employed to evaluate the sensitisation potential the substance (0.25%, 0.5% or 0.75%) was administered topically to guinea pigs (20 animals/concentration) once each week for a 3 week induction period. Twenty seven days after the first induction dose, a challenge dose of the test substance at its highest non-irritating concentration was applied to a naive site on each guinea pig. A naive control group (ten animals) was maintained under the same environmental conditions and treated with the substance at challenge only. The animals were scored for erythma approximately 24 hours and 48 hours after each induction and challenge dose. Based on the results of this study, the substance is not considered to be a contact sensitiser.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

28th January 1987 - 20th March 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

equivalent or similar to guideline

Guideline:

other: the protocol of Guillot-Gonnet-Clément-Brulos published by the AFNOR: FD n° T03-300

Deviations:

no

Principles of method if other than guideline:

Guinea-pig maximisation test.

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The guinea-pig maximisation study was conducted prior to LLNA methodology availability.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Various
- Females nulliparous and non-pregnant:[yes
- Weight at study initiation: 300 to 500 g
- Housing: Polystyrene cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum of 5 days before the begining of treatment
- Indication of any skin lesions: none.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 30 to 70% RH
- Photoperiod (hrs dark / hrs light): a 12-hour light-dark cycle

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

0.2% w/v at 0.5 mL

Day(s)/duration:

Initial application

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

5% w/v in 0.5 mL

Day(s)/duration:

Every 48 hours following initial application for a total of 7 applications.

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

0.2% w/v at 0.5 mL

Day(s)/duration:

48 hours

No. of animals per dose:

10/sex
1/sex untreated.

Details on study design:

RANGE FINDING TESTS: A minimum of one treated group of 2 males and 2 females were dosed 0.5 mL (this being the maximum quantity applicable under an occlusive patch) of concentrations of 100% and 0.2% w/v in water . Two concentrations per animal were administered to clipped skin on the dorsal area for 48 hours and kept in contact with the skin under an occlusive patch. The substance was applied once and cutaneous examinations were carried out 6, 24 and 48 hours after removal of the patches.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 7 exposures.
- Exposure period: 48 hours.
- Test groups: 1 test group
- Control group: 1 control group
- Site: clipped upper thoracic region, just behind the right scapulum.
- Frequency of applications: every 48 hour
- Concentrations: 0.5 mL

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Exposure period: 48 hours
- Test groups: 1
- Control group: 1
- Site: untreated region of the abdominal lateral region.
- Concentrations: 0.5 mL
- Evaluation (hr after challenge): 6, 24 and 48 hours after removal of the occlusive patch.

Challenge controls:

Untreated animal served as controls because the substance was used as supplied (i.e. no vehicle).

Positive control substance(s):

no

Positive control results:

Not applicable.

Key result

Reading:

1st reading

Hours after challenge:

6

Group:

test chemical

Dose level:

5% w/v challenge

No. with + reactions:

3

Total no. in group:

20

Clinical observations:

None.

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

24

Group:

test chemical

Dose level:

5% w/v challenge

No. with + reactions:

0

Total no. in group:

17

Clinical observations:

None

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

other: 3rd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

5% w/v challenge

No. with + reactions:

0

Total no. in group:

17

Clinical observations:

None

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

The substance at 5% w/v not produce any cutaneous sensitising reaction (nil or very weak) in 19 out of 20 animals in the guinea pig maximisation test.

Executive summary:

In an amended guinea pig maximisation test to evaluate the sensitisation potential of the substance male and female mice (ten animals/sex) were exposed (occlusive) topically to the substance at 0.2% w/v in water during first application followed by 7 topical (occlusive) applications at 5% w/v in water every 48 hours. Following a resting period of 12 days a challenge application was administered topically for 48 hours employing 0.2% w/v in water at 0.5 mL a site away from the site of initial induction. The skin site was monitored for any signs of irritation at 6, 24 and 48 hours post-application. A skin biopsy was taken from those animals in which irritation was observed at 6 hours following the challenge application. Macroscopic and histological evaluations were conducted on these tissues. No other animals exibited signs of irritation for the remainder of the study. Macroscopic and histological evaluations were conducted on these tissues as well. The findings indiacte that the substance is not a skin sensitiser or is a weak sensitiser as reported by the study facilitator.

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

21 June 2004 - 30th july 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

The study was conducted for non-EU REACH purposes.

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: #D4223025

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Stored at RT
- Stability under test conditions: Expected to be stable for the duration of the test
- Solubility and stability of the test substance in the solvent/vehicle: Soluble in distilled water

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Elm Hill Breeding Labs, Chemlsford, MA.
- Females nulliparous and non-pregnant: yes
- Weight at study initiation: Young adult males 312 - 365 g and females 313 - 380 g.
- Housing: Suspended stainless steel caging with mesh floors or perforated bottom caging.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6, 27 or 31 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-24°C
- Humidity (%): 50-70%
- Photoperiod (hrs dark / hrs light): 12-hour lightt/dark cycle

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

0.25%, 0.5% or 0.75% - induction phase
0.1% - challenge phase

Day(s)/duration:

Induction phase was conducted once each week for 3 weeks.

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

0.1%

Day(s)/duration:

Challenge phase was conducted 27 days after the first induction dose. These sites were evaluated for a sensitisation response approximately 24 and 48 hours aftter the challenge application.

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

20 animals/dose

Challenge controls:

Ten guinea pigs were maintained under identical environmental conditions and distilled water was applied to a naive site on the right side of each animal as a challenge dose. The test substance was applied during challenge.

Positive control substance(s):

no

Key result

Hours after challenge:

24

Group:

negative control

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Key result

Hours after challenge:

48

Group:

negative control

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Key result

Hours after challenge:

24

Group:

test chemical

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

no indication of skin sensitisation

Key result

Hours after challenge:

48

Group:

test chemical

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

no indication of skin sensitisation

	Sensitisation Response Indices
	Incidence of Positive Response		Severity
	24 hours	48 hours	24 hours	48 hours
Test Animals	0/20	0/20	0.1	0.05
Naive Control Animals	0/10	0/10	0.2	0.05

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is not a skin sensitiser.

Executive summary:

In a Beuhler assay to evaluate the sensitisation potential the substance (0.25%, 0.5% or 0.75%) was administered topically to guinea pigs (20 animals/concentration) once each week for a 3 week induction period. Twenty seven days after the first induction dose, a challenge dose of the test substance at its highest non-irritating concentration was applied to a naive site on each guinea pig. A naive control group (ten animals) was maintained under the same environmental conditions and treated with the substance at challenge only. The animals were scored for erythma approximately 24 hours and 48 hours after each induction and challenge dose. Based on the results of this study, the substance is not considered to be a contact sensitiser.

Reference 3

Endpoint:

skin sensitisation: in chemico

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the available information indicates that the substance should be classified for respiratory sensitisation or corrosivity

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The substance is corrosive and so this endpoint can be waived. However, the findings of two reliable in vivo skin sensitisation studies conducted on a structurally similar substance, support the conclusion that classification of the substance is not justified.