Poly(oxy-1,2-ethanediyl), α-[2-(dide- cylmethylammonio)ethyl]- .omega.- hydroxy-, propanoate (salt) (Bardap 26)

Endpoint summary

Description of key information

Bardap 26 was not a skin sensitiser in the Buehler guinea-pig test.

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:

25 August to 30 September 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

Principles of method if other than guideline:

Not applicable.

GLP compliance:

yes (incl. QA statement)

Type of study:

Buehler test

Justification for non-LLNA method:

In the year 1994 the Buehler Test was a common valid test system for testing of sensitising potential.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

The test animals were female Dunkin-Hartley guinea pigs obtained from David Hall Limited, Staffordshire, UK. The guinea pigs were 8-12 weeks old at study initiation and weighed 330 - 440 g. The animals were acclimatised for at least 5 days. They were housed in groups of up to 2 in solid-floor polypropylene cages furnished with woodflakes. The animal room was maintained at a temperature of 19-24°C and relative humidity of 58-67%. There were approximately 15 air changes per hour and lighting was provided on a 12 hour light/dark cycle.
In-life dates: 25 August to 30 September 1994.

Route:

epicutaneous, occlusive

Vehicle:

water

Remarks:

distilled

Concentration / amount:

1% v/v in distilled water

Day(s)/duration:

1

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

water

Remarks:

distilled

Concentration / amount:

1% and 0.5% v/v in distilled water

Day(s)/duration:

1, 2

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

Treatment group: 20 guinea pigs
Controls: 10 guinea pigs
Positive controls: 20

Details on study design:

Range finding - topical induction
Two previously untreated guinea pigs were treated with 0.5 ml of the undiluted test material and three concentrations in distilled water (75%, 50% and 25% v/v). These animals were killed for humane reasons immediately after dressing removal due to severe dermal necrosis. Two more guinea pigs were treated with the test substance in distilled water at 10%, 5%, 2% and 1% v/v. The highest concentration of the test substance producing only mild irritation after a 6 hour occlusive dermal exposure was selected for the topical induction stage of the main study.

Range finding - topical challenge
Two guinea pigs were treated with 0.5 ml of each of four concentrations of the test material in distilled water (2%, 1%, 0.5% and 0.2% v/v). The highest concentration of the test substance which produced no evidence of dermal irritation 24 or 48 hours after a 6 hour occlusive dermal exposure and one lower concentration were selected for the topical change stage of the main study.

Main study - Induction
The hair was clipped from an area of the left flank of each animal. 0.5 ml of the test substance (1% v/v in distilled water) was applied topically on absorbent lint, which was was held in place under a strip of surgical adhesive tape and covered with an overlapping length of aluminium foil. The patch and foil were further secured with Elastoplast wound in a double layer around the torso. The occlusive dressing was kept in place for 6 hours. The induction procedure was repeated on the same site on Day 7 and 14 for a total of three 6 hour exposures. Approximately 24 hours after each induction application (days 1, 8 and 15) the sites were assessed for erythema and oedema formation. Controls were exposed in an identical manner, but with vehicle alone.

Main study - Challenge
Prior to treatment on day 28, the fur was clipped from the right flank of each animals. 0.5 ml of the test substance (1% v/v in distilled water) was applied to the shorn right flank on absorbent lint which was held in place by a strip of surgical adhesive tape. To ensure that the maximum non-irritant concentration was used at challenge, the test material at 0.5% v/v in distilled water was also similarly applied to a separate skin site on the right shorn flank. The patches were occluded as above. After 6 hours, the dressings were removed. The treatment sites were rinsed with distilled water and treatment sites marked using indelible marker. On Day 29 the flanks were clipped free of hair. Erythema and oedema formation was assessed approximately 24 and 48 hours after dressing removal.

Challenge controls:

Yes - controls were induced and challenged with the vehicle alone (distilled water).

Positive control substance(s):

yes

Remarks:

2,4-dinitrochlorobenzene (DNCB)

Positive control results:

11 out of 20 animals (55%) affected, indicative of a satisfactory skin sensitisation response.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.5%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

No with. + reactions: 0.0. Total no. in groups: 20.0.

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.5%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5% v/v. No with. + reactions: 0.0. Total no. in groups: 20.0.

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1.0%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

Slight erythema in two test animals

Remarks on result:

positive indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1.0%

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1.0% v/v. No with. + reactions: 0.0. Total no. in groups: 20.0.

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

eading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0% (distilled water). No with. + reactions: 0.0. Total no. in groups: 10.0.

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0% (distilled water). No with. + reactions: 0.0. Total no. in groups: 10.0.

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: no positive control used

Table 1. Mean body weight (g)

Day of study	Test animals	Control animals
0	380.5	392.8
30	628.25	651.9
Mean increase	247.75	259.1

 

Table 2. Skin responses at induction

Day of study	Erythema		Oedema
	Test animals	Controls	Test animals	Controls
1	0 (1) 1 (6) 2 (13)	0 (10)	0 (1) 1 (18) 2 (1)	0 (10)
8	1 (11) 2 (9)	0 (10)	0 (1) 1 (19)	0 (10)
15	0 (3) 1 (14) 2 (3)	0 (10)	0 (15) 1 (5)	0 (10)

Grade (number of animals affected)

 

Table 3. Skin responses at challenge

	Test animals								Control animals
Test material conc.	1.0% v/v				0.5% v/v				0% (distilled water)
Observation time (hours)	24		48		24		48		24		48
Parameter^#	E	O	E	O	E	O	E	O	E	O	E	O
Scores (incidence)	0 (18) 1 (2)	0 (20)	0 (20)	0 (20)	0 (20)	0 (20)	0 (20)	0 (20)	0 (10)	0 (10)	0 (10)	0 (10)

^#E = erythema; O = oedema

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance was not sensitising to guinea pigs, and therefore does not require classification as a skin sensitiser.

Executive summary:

The skin sensitising properties of Bardap 26 were evaluated in a guinea pig Buehler test. Twenty guinea pigs were given 3 topical (occlusive) induction applications of the test substance at a concentration of 1.0% v/v (Days 0, 7 and 14), followed by a single topical (occlusive) challenge (of 0.5 and 1.0% v/v) two weeks after the last induction (Day 28). Ten guinea pigs were exposed to the vehicle (distilled water) only at both induction and challenge.

There were no mortalities during the study, and mean body weight gain was comparable between treated and control groups. There was no evidence of skin sensitisation in any test animal. Very slight to well-defined erythema with or without very slight to slight oedema was seen in two test animals at 24 hours after challenge with 1.0% v/v. No reactions were seen after 48 hours therefore the responses at 24 hours were considered to be due to irritation. No reactions were seen after challenge with 0.5% v/v. It was concluded that the test substance is not a skin sensitiser. No classification is required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Bardap 26 was not a skin sensitiser in the Buehler guinea-pig test (Allen, 1994).

Migrated from Short description of key information:
A high quality, guideline- and GLP-compliant study is available.

Justification for selection of skin sensitisation endpoint:
Only one study is available for this endpoint.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Bardap 26 was not a skin sensitiser in the Buehler guinea-pig test (Allen, 1994).

Justification for classification or non-classification

The substance was not a skin sensitiser in the Buehler guinea-pig test (Allen, 1994), and therefore classification is not required according to CLP criteria.