Paraquat-dichloride

Endpoint summary

Description of key information

The test substance is not considered to be sensitising to the skin, based on the GLP compliant study similar to OECD TG 406.

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:

May 1994 to Jul 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Principles of method if other than guideline:

The sensitisation of the test sample was assessed using a method based on the maximisation test of Magnusson and Kligman (1970).

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Currently no LLNA study is available for assessment. The Guinea Pig Maximization Test (GPMT) has been carried out as an animal test to predict human sensitization for over a decade and is recommended by international test guidelines such as OECD.

Species:

guinea pig

Strain:

other: Albino guinea pigs (Hsd/Poc:DH)

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Age at study initiation: young adults
- Weight at study initiation: 411 to 537 g
- Housing: individually in suspended stainless steel cages (32.5cm length x 37.5cm width x 23cm height), with solid sheet sides and wire mesh floor and front. The rear was made of vented sheet
- Diet: ad libitum , RGP Diet
- Water: ad libitum
- Acclimation period: 6 days prior to each study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): approximately 25 to 30
- Photoperiod (hrs dark / hrs light): 12 / 12

Route:

intradermal

Vehicle:

water

Concentration / amount:

10 %w/v
30 %w/v

Day(s)/duration:

24 h and 48 h

Adequacy of induction:

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

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

10 %w/v

Day(s)/duration:

24 h and 48 h

Adequacy of induction:

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

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

30 %w/v test group
10 %w/v control group

Day(s)/duration:

24 h and 48h

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

- 20 test group and positive control group
- 10 negative control group

Details on study design:

RANGE FINDING TESTS:
The objective of the sighting study was to determine suitable levels for use in the main study. Suitable levels were ones which gave an acceptable degree of irritation and did not give rise to signs of overt systemic toxicity under the conditions of the test. On the basis of skin irritation and systemic toxicity observed in the sighting study, main study dose-levels were selected as described in the main study.

MAIN STUDY
INDUCTION EXPOSURE
Induction A: intradermal, test group: Induction of the test animals was performed by removing the hair with a pair of veterinary clippers from an area approximately 5cm x 5cm on the scapular region of each animal. Subsequently, a row of three injections (0.05-0.1 mL each) was made on each side of the mid-line. The injections were:
- Top: Freund’s Complete Adjuvant plus deionised water in the ratio 1:1;
- Middle: a 0.03% w/v preparation of the test sample in deionised water (the highest concentration which could be tolerated without causing necrosis of the skin at the injection sites);
- Bottom: a 0.03% w/v preparation of the test sample in a 1:1 preparation of Freund's Complete Adjuvant plus deionised water.

Induction A: intradermal, control group: intradermal injections were administered using an identical procedure to that used for the test animals, except that the injections were:
- Top: Freund's Complete Adjuvant plus deionised water in the ratio 1:1;
- Middle: deionised water;
- Bottom: Freund's Complete Adjuvant plus deionised water in the ratio 1:1.

Induction B: epicutaneous, test group: One week later, the scapular area was clipped again and treated with a topical application of the test sample as a 10% w/v preparation (the highest concentration which could be applied topically over the intradermal injection sites without causing signs of toxicity) in deionised water. This preparation (0.2-0.3mL) was applied on filter paper (approximate size 4cm x 2cm) which was held in place by a piece of surgica1 tape. The tape was covered by a strip of adhesive bandage (approximate size 20-30cm x 5cm) and secured by a piece of self-adhesive PVC tape. This occlusive dressing was kept in place for approximately 48 hours. The application sites were checked approximately 24 hours after removal of the dressings.

Induction B: epicutaneous, control group: The topical applications followed the same procedure as for the test animals except that deionised water only was applied to the filter paper.

CHALLENGE EXPOSURE
Two weeks after the topical inductions, an area, approximately 15cm x 5cm, on both flanks of all the test and control animals, was clipped free of hair with a pair of veterinary clippers. An occlusive dressing was prepared which consisted of two pieces of filter paper (approximate size 1cm x 1.5-2.0cm) stitched to a piece of rubber sheeting (approximate size 12cm x 5cm). A 30% w/v preparation (the highest concentration which could be applied without causing skin irritation) of the test sample in deionised water (0.05-0.1 mL) was applied to one of the pieces of filter paper and a 10% w/v preparation in deionised water (0.05-0.1 mL) was applied to the second piece of filter paper. The dressing was placed on to the guinea pig so that the 30% w/v preparation was on the left shorn flank and the 10% w/v preparation was on the right shorn flank. It was then covered with a strip of adhesive bandage (approximate size 25-40cm x 7.5cm) which was secured by a self-adhesive PVC tape. After approximately 24 hours, the dressings were carefully cut, using blunt-tipped scissors, removed and discarded. The position of the pieces of filter paper on the skin were identified using a black waterproof marker pen. The application sites were cleansed free of any residual test sample using clean swabs of absorbent cotton wool soaked in clean arm water and was then dried gently with clean tissue paper. Erythematous reactions were quantified and recorded using the four-point scale (shown in Table 1 in “Any other information on materials and methods incl. tables”) approximately 24 and 48 hours after removal of the dressings. Where necessary animals were re-clipped prior to the 1 day reading.

SCORING
To classify the sensitisation repsonse, the percentage of the control animsl that responded was substracted form the percentage of the test animals that responded. This responsed was compared with the scheme presented in Table 2 in "Any other informaiton on materials and methods incl tables".

POSITIVE CONTROL STUDY
The sensitising potential of 2-mercaptobenzothiazole was assessed at the following concentrations:
- 3% w/v preparation in corn oil was used for the intradermal injections
- 75% w/v preparation in corn oil was applied for the topical induction
- 30% w/v preparation in corn oil was applied for the challenge phase

Positive control substance(s):

yes

Remarks:

2-Mercaptobenzothiazole

Positive control results:

Following challenge with a 30% w/v preparation of 2-mercaptobenzothiazole, scattered mild redness or moderate and diffuse redness was observed in nineteen test animals. There was no erythematous response in any of the control animals. The net percentage response was calculated to be 95%.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10 %(w/v)

No. with + reactions:

0

Total no. in group:

20

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

30 %w/v

No. with + reactions:

0

Total no. in group:

20

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

10 %w/v

No. with + reactions:

0

Total no. in group:

10

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

30 %w/v

No. with + reactions:

0

Total no. in group:

10

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

30 %w/v

No. with + reactions:

17

Total no. in group:

20

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

30 %w/v

No. with + reactions:

18

Total no. in group:

20

One test animal was found dead following the topical induction. The reason for the death is not known but in the absence of any signs of toxicity in any of the animals it is considered to be unrelated to treatment.

Following challenge with a 30% or a 10% w/v preparation of the test sample in deionised water, there was no erythematous reaction in any of the test or control animals. Initial and final bodyweights indicated that all of the animals exhibited normal growth during the study.

Interpretation of results:

GHS criteria not met

Conclusions:

In this study performed similarly to OECD 406, the test substance was not considered to be sensitising to the skin.

Executive summary:

In this GLP compliant study the sensitisation potential of the test substance was assessed using a method based on the maximisation test of Magnusson and Kligman (1970). Challenge of previously induced guinea pigs with 30% or 10% w/v preparations of the test sample in deionised water did not elicit a skin sensitisation response. In a positive control study, challenge of previously induced guinea pigs with a 30% w/v preparation of 2-mercaptobenzothiazole elicited an extreme skin sensitisation response. In conclusion, the test substance was not a skin sensitiser under the conditions of the test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In a GLP compliant study (Duerden, 1994) the sensitisation potential of the test substance was assessed using a method based on the maximisation test of Magnusson and Kligman (1970). Challenge of previously induced guinea pigs with 30% or 10% w/v preparations of the test sample in deionised water did not elicit a skin sensitisation response. In a positive control study, challenge of previously induced guinea pigs with a 30% w/v preparation of 2-mercaptobenzothiazole elicited an extreme skin sensitisation response. In conclusion, the test substance was not a skin sensitiser under the conditions of the test.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available information, classification for skin sensitisation is not warranted in according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.