Fenitrothion

Endpoint summary

Description of key information

Two guinea pig studies of skin sensitisation are available for fenitrothion.

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:

No data (published article)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

Maximisation

GLP compliance:

no

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Published literature study; performed prior to the adoption of OECD TG 429

Specific details on test material used for the study:

Fenitrothion: no additional details reported

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Route:

intradermal

Vehicle:

water

Concentration / amount:

5%

Day(s)/duration:

Not reported

Adequacy of induction:

not specified

Route:

other: dermal

Vehicle:

water

Concentration / amount:

25%

Day(s)/duration:

Not reported

Adequacy of induction:

not specified

No.:

#1

Route:

other: dermal

Vehicle:

water

Concentration / amount:

0.5%, 5%

Day(s)/duration:

Not reported

Adequacy of challenge:

not specified

No. of animals per dose:

10

Details on study design:

0.5% (challenge), 5% (intradermal induction and challenge) or 25% (dermal induction) fenitrothion in distilled water was applied. Induction and challenge were undertaken according to the original method. Skin reactions were observed 24 and 48 hours after removal of the patch, and the results were graded using a procedure by Kligman.

Challenge controls:

No data

Positive control substance(s):

not specified

Positive control results:

Not reported

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.5%

No. with + reactions:

3

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.5%

No. with + reactions:

4

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

5%

No. with + reactions:

7

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

5%

No. with + reactions:

7

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Remarks on result:

not measured/tested

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Remarks on result:

not measured/tested

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Remarks on result:

not measured/tested

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Remarks on result:

not measured/tested

Summary of dermal reactions

Name	Challenge concentration	Response (%)
		24h	48h
Fenitrothion	5%	70	70
	0.5%	30	40

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

Based on the results of this study (sensitisation of >=30% in response to an intradermal induction of >1.0%), fenitrothion is considered to be a moderate sensitiser and is classified as a skin sensitiser in Category 1B according to the CLP Regulation.

Executive summary:

The skin sensitisation potential of fenitrothion was investigated in a published guinea pig Maximisation study. Groups of guinea pigs were induced using intradermal injection of 5% fenitrothion (in distilled water) and dermal application of 25% fenitrothion. All animals were subject to dermal challenge using 0.5% and 5% fenitrothion; dermal reactions were assessed at 24 and 48 hours following the challenge application. At 24 hours, positive responses were reported for 30% of the animals exposed to 0.5% fenitrothion and 70% of the animals exposed to 5% fenitrothion. At 48 hours, positive responses were reported for 40% of the animals exposed to 0.5% fenitrothion and 70% of the animals exposed to 5% fenitrothion. The study therefore indicates that fenitrothion is a skin sensitiser and requires classification as a skin sensitiser in Category 1B according to the CLP Regulation.

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1 July 1972 - 20 August 1972

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: Sacchuzai Shi-shin (Guideline for toxicity testing of insecticides for sanitary use, Japan) equivalent to Landsteiner-Draize’s method

Deviations:

no

GLP compliance:

no

Type of study:

other: Landsteiner-Draize method

Justification for non-LLNA method:

The study was performed prior to the development and adoption of the LLNA

Specific details on test material used for the study:

Fenitrothion
Batch No.: 417
Purity: 97.2%

Species:

guinea pig

Strain:

not specified

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Nihon Dobutsu Co., Osaka
- Weight at study initiation: 250-300 g
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23-27
- Humidity (%): 50-70

Route:

intradermal

Vehicle:

corn oil

Concentration / amount:

0.1 mL of a 1% or 5% solution

Day(s)/duration:

Ten injections, on alternate days

Adequacy of induction:

not specified

No.:

#1

Route:

intradermal and epicutaneous

Vehicle:

corn oil

Concentration / amount:

0.05 mL by intradermal injection or 0.03 mL dermal application; 1% or 5% solution

Day(s)/duration:

Single exposure

Adequacy of challenge:

not specified

No. of animals per dose:

6

Details on study design:

0.1 ml of a 1% or 5% solution of fenitrothion in corn oil was injected intradermally to the back of animals, every other day for a total of 10 injections (except that 0.05 ml was used in the first sensitizing treatment). Two weeks after the last sensitizing injection, each animal was challenged by intradermal injection (0.05 ml) and dermal application (0.03 ml) of the same concentration as used for sensitizing injections. As a positive control, 0.1 ml of 0.05% DNCB (2,4-dinitrochlorobenzene) dissolved in corn oil was treated in the same way as fenitrothion, except that the sensitizing treatments were conducted 3 times every other day. The animals were challenged with 0.1% DNCB (intradermal injection), 0.3% (dermal application) and 1.0% (dermal application) as in the treated groups. Three negative control groups received corn oil as induction treatment. The animals were challenged with 5% fenitrothion (intradermal injection and dermal application), corn oil (intradermal injection), or DNCB (0.1%; intradermal injection, 1%; dermal application) as in the treated groups.

Challenge controls:

Corn oil

Positive control substance(s):

yes

Remarks:

DNCB

Positive control results:

In the animals sensitized and challenged with DNCB (intradermal injection or dermal application), haemorrhage and oedema were observed.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

5%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

DNCB, 1%

No. with + reactions:

5

Total no. in group:

5

Remarks on result:

positive indication of skin sensitisation

Summary of dermal reactions

Group		A	B	C1	C2	C3	C4	D1	D2	D3
Induction:		Fenitrothion	Fenitrothion	Corn oil				DNCB
Challenge:		Fenitrothion	Fenitrothion	Corn oil	Fenitrothion	DNCB		DNCB
Concentration (%)		1	5	-	5	0.1	1	0.1	0.3	1
Number of animals used		6	6	3	3	3	3	5	5	5
Reactions	-	6/6	1/6	3/3	0/3	1/3		0/5
(intradermal	±	0/6	5/6	0/3	3/3	2/3		0/5
injection)	+	0/6	0/6	0/3	0/3	0/3		3/5
	++	0/6	0/6	0/3	0/3	0/3		2/5
	+++	0/6	0/6	0/3	0/3	0/3		0/5
Reactions	-	6/6	6/6		3/3		3/3		0/5	0/5
(dermal	±	0/6	0/6		0/3		0/3		0/5	0/5
application)	+	0/6	0/6		0/3		0/3		0/5	0/5
	++	0/6	0/6		0/3		0/3		3/5	0/5
	+++	0/6	0/6		0/3		0/3		2/5	5/5

-: No sign

±: Very slight swelling and erythema

+: Slight swelling and hyperaemia,

++: Moderate swelling and hyperaemia

+++: Severe swelling and hyperaemia

Interpretation of results:

GHS criteria not met

Conclusions:

There was no evidence of skin sensitisation in this study; fenitrothion is not therefore classified as a skin sensitiser on the basis of this study.

Executive summary:

The skin sensitisation potential of fenitrothion was investigated in a guinea-pig study following the Landsteiner-Draize method. 0.1 ml of a 1% or 5% solution of fenitrothion in corn oil was injected intradermally to the back of animals, every other day for a total of 10 injections (except that 0.05 ml was used in the first sensitizing treatment). Two weeks after the last sensitizing injection, each animal was challenged by intradermal injection (0.05 ml) and dermal application (0.03 ml) of the same concentration as used for sensitizing injections.  As a positive control, 0.1 ml of 0.05% DNCB (2,4-dinitrochlorobenzene) dissolved in corn oil was treated in the same way as fenitrothion, except that the sensitizing treatments were conducted 3 times every other day. The animals were challenged with 0.1% DNCB (intradermal injection), 0.3% (dermal application) and 1.0% (dermal application) as in the treated groups.  Three negative control groups received corn oil as induction treatment. The animals were challenged with 5% fenitrothion (intradermal injection and dermal application), corn oil (intradermal injection), or DNCB (0.1%; intradermal injection, 1%; dermal application) as in the treated groups. In the animals sensitized and challenged with DNCB (intradermal injection or dermal application), haemorrhage and oedema were observed. There was no evidence of skin sensitisation in this study. Findings of swelling and slight hyperaemia seen following intradermal challenge with 5% fenitrothion were considered to be due to primary irritation. Fenitrothion is not therefore classified as a skin sensitiser on the basis of this study.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

An older non-guideline study reports a negative result; a published Maximisation assay reports a positive result.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Fenitrothion has a harmonised classification under CLP and is not classified as a skin sensitiser. The results of the key (Maximisation) study indicates a potential for skin sensitisation; therefore classification for skin sensitisation is proposed for fenitrothion. Based on the results of the key study (sensitisation of >=30% in response to an intradermal induction of >1.0%), fenitrothion is considered to be a moderate sensitiser and is classified as a skin sensitiser in Category 1B according to the CLP Regulation.