Dipropoxymethane

Endpoint summary

Description of key information

Propylal is not sensitizing in test performed according to OECD TG 406 and GLP.

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:

key study

Study period:

From 01 June 2012 to 20 July 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

Adopted 17 July 1992

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study performed according to M&K was already available.

Species:

guinea pig

Strain:

Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories France, L’Arbresle, France
- Females (if applicable) nulliparous and non-pregnant: yes
- Microbiological status of animals, when known: Caesarian obtained, Barrier sustained - Virus Antibody Free (COBS - VAF®)
- Age at study initiation:1 to 2 months old
- Weight at study initiation: mean body weight of 293 g (range: 259 g to 517 g)
- Housing: The animals were individually housed in polycarbonate cages with stainless steel lid (Tecniplast 2154, 940 cm²) containing autoclaved sawdust (SICSA, Alfortville, France).
- Diet (e.g. ad libitum): 106 pelleted maintenance diet, batch No. 12010, (SAFE, Augy, France)
- Water (e.g. ad libitum): tap water (filtered with a 0.22 μm filter)
- Acclimation period: at least 5 days before treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h

Route:

intradermal

Vehicle:

corn oil

Concentration / amount:

10 %

Day(s)/duration:

On day 1

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Route:

epicutaneous, occlusive

Vehicle:

other: ethanol/drinking water treated by reverse osmosis (80/20)

Concentration / amount:

100 %

Day(s)/duration:

On day 8 for 48 hours

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Route:

epicutaneous, occlusive

Vehicle:

other: acetone

Concentration / amount:

50 %

Day(s)/duration:

On day 22 for 24 hours

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

Preliminary test: 4 females
Main test :15 females

Details on study design:

Induction phase - intradermal injections:
On day 1, the dose formulations were administered by intradermal injection in the clipped interscapular region using a sterile plastic syringe fitted with a sterile single use needle.
A constant dosage-volume of 0.1 mL/injection was used.
The dose formulations were stirred continuously throughout the dosing procedure.
Three pairs of injections were given so that one of each pair lies on each side of the midline.
- Freund's Complete Adjuvant (FCA) diluted to 50% (v/v) with 0.9% NaCl,
- test item in vehicle or vehicle alone,
- test item in FCA/0.9% NaCl (50/50, w/w) or vehicle at 50% (w/v) in FCA/0.9% NaCl (50/50, v/v).
The first and second pairs of injections were given close to each other and nearest the head, while the third pair was given towards the caudal part of the test area.

Induction phase - topical application:
On day 8, a filter paper (approximately 8 cm²) was fully-loaded with the dose formulations, and then applied to the clipped interscapular region, over the intradermal injection sites.
The filter paper was held in place by means of an occlusive dressing for 48 hours.
Control animals received the drinking water treated by reverse osmosis only.
On removal of the dressing, no residual test item was observed.
The presence of local irritation was checked (but not scored).
The induction phase was followed by a 14-day rest period.

Challenge phase:
On day 22, a Finn Chamber® filter paper was fully-loaded with the dose formulations.
The test item dose formulations were applied to the shaved posterior right flank of animals and the vehicle was applied to the shaved posterior left flank.
The chamber was held in contact with the skin by an occlusive dressing for 24 hours.
On removal of the dressing, any residual dose formulation was removed using a cotton pad moistened with drinking water treated by reverse osmosis.
Cutaneous reactions were evaluated before treatment and 24 and 48 hours after removal of the dressing.

Positive control substance(s):

yes

Remarks:

The sensitivity and reliability of the experimental technique used is assessed every 6 months by performing the test with the reference item Benzothiazole-2-thio and checking that at least 30% of responses are positive.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

Induction concentration: intradermal injection day 1 = 0%, cutaneous application day 8 = 0%; Challenge concentration day 22: Left flank = 0%, right flank = 50%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

IInduction concentration: intradermal injection day 1 = 0%, cutaneous application day 8 = 0%; Challenge concentration day 22: Left flank = 0%, right flank = 50%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

Induction concentration: intradermal injection day 1 = 10%, cutaneous application day 8 = 100%; Challenge concentration day 22: Left flank = 0%, right flank = 50%

No. with + reactions:

2

Total no. in group:

10

Clinical observations:

Discrete erythema (grade 1)

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

Induction concentration: intradermal injection day 1 = 10%, cutaneous application day 8 = 100%; Challenge concentration day 22: Left flank = 0%, right flank = 50%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

- No unscheduled deaths occurred during the main test.

- No clinical signs indicative of systemic toxicity were observed in any animals. Marked local reactions (but no necrosis) at the intradermal injection sites were noted in all animals of both groups from day 6, 7 or 8 until the end of the study period.

- In the control group, at the 24- and 48-hour readings, no cutaneous reactions were observed at left flank (treated with acetone) and at right flank (treated with test item) of animals.

In the test item-treated group, at the 24-hour reading, a discrete erythema (grade 1) was noted at right flank (treated with test item) of only 2/10 animals. In addition, these cutaneous reactions did not persist at the 48-hour reading. Therefore, they were considered not to be attributed to delayed contact hypersensitivity.

- The body weight of the animals was unaffected by the test item-treatment

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions of this study, the test item, Propylal, did not induce delayed contact hypersensitivity in guinea pigs. Therefore, the test item should not be considered as a skin sensitizer.

Executive summary:

The objective of this study was to evaluate the potential of the test item, Propylal, to induce delayed contact hypersensitivity in guinea pigs.

Methods:

Two preliminary tests were first performed in order to determine the test item concentrations to be used in the main test.

In the main test, one group of ten females received the test item:

- on day 1 by intradermal injections in the interscapular region at the concentration of 10%,

- on day 8 by topical application to the clipped interscapular region at 100%,

- on day 22 by topical application to the posterior right flank at 50%. The posterior left flank of the animals received the vehicle.

Another control group of five females received the vehicles:

- corn oil on day 1 in the interscapular region,

- ethanol/drinking water treated by reverse osmosis on day 8 in the interscapular region,

- acetone on day 22 to the posterior left flank. The posterior right flank of animals received the test item at 50%.

On day 1, three pairs of intradermal injections were performed in the interscapular region of animals:

- Freund's Complete Adjuvant (FCA) diluted to 50% (v/v) with 0.9% NaCl,

- test item in vehicle or vehicle alone,

- test item in FCA/0.9% NaCl (50/50, w/w) or vehicle at 50% (w/v) in FCA/0.9% NaCl (50/50, v/v).

On day 8, a filter paper (approximately 8 cm²) was fully-loaded with the dosage forms, and then applied to the clipped interscapular region, over the intradermal injection sites. The filter paper was held in place by means of an occlusive dressing for 48 hours. The presence of local irritation was checked (but not scored). The induction phase was followed by a 14-day rest period.

On day 22, a Finn Chamber® filter paper was fully-loaded with the dosage forms. The chamber was held in contact with the skin by an occlusive dressing for 24 hours. Cutaneous reactions were evaluated before treatment and 24 and 48 hours after removal of the dressing. Each animal was observed at least once a day for mortality and clinical signs during the treatment and observation periods. Body weight was recorded on day 1 and at the end of each observation period. On completion of the observation period, the animals were sacrificed then discarded without macroscopic post-mortem examination. No skin samples were preserved.

Results:

After the challenge application, no cutaneous reactions were observed on the left flank (treated with acetone) and on the right flank (treated with the test item) of control animals.

In the test item-treated group, at the 24-hour reading, a discrete erythema (grade 1) was noted at right flank (treated with test item) of only 2/10 animals. In addition, these cutaneous reactions did not persist at the 48-hour reading. Therefore, they were considered not to be attributed to delayed contact hypersensitivity.

Conclusion:

Under the experimental conditions of this study, the test item, Propylal, did not induce delayed contact hypersensitivity in guinea pigs. Therefore, the test item should not be considered as a skin sensitizer.

Reference 2

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available

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

not classified for skin sensitizing hazard based on CLP criteria.