Chlorothalonil

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Type of information:

other: Human data

Adequacy of study:

other information

Study period:

2016

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Study type:

other: Overview of available human data

Test guideline

Qualifier:

no guideline required

GLP compliance:

no

Applicant's summary and conclusion

Conclusions:

In summary, there have been few reports in the literature of adverse responses in humans to the test substance. Most of the reported effects can be linked to the irritation potential of the technical material, although it must be noted that there was little work carried out to differentiate between irritation and sensitisation.
Although the absence of evidence of skin effects is not evidence of absence of effects, the test substance have been extensively used for over 30 years, in a variety of applications. If the skin sensitising potential was high, then a greater number of reports would been expected. Although the formulations with the test substance have the potential to cause skin sensitisation in humans, the data from over 30 years of practical use show that it is of low potency.

Executive summary:

SKIN SENSITISATION - HUMAN DATA
Formulations with the test substance have the potential to cause significant skin irritation in animals, particularly where contact is repetitive or extended. Such irritation often complicated the assessment of animal skin sensitisation studies.

This review examines the reported incidence of skin sensitisation reactions in man. As in animals, the assessment is complicated by findings of irritancy. However, the incidence of skin findings overall is low, and the incidence of confirmed skin sensitisation lower still. It can be concluded that human skin sensitisation by the test substance can occur, but both incidence and severity are low.

 

The following sources have been reviewed for information on reported adverse skin effects in humans following the normal use of the fungicide product with the test substance:

- Companies adverse incident database

- US FASTMED database

- The National Poisons Information Service (London) database

- California Pesticide Illness Surveillance database

- The published scientific literature

 

Experience in Use
1. Companies adverse incident data.

A database has been kept since the early 1970s on alleged adverse health effects arising from the use, misuse and abuse of its products. To date this database contains over 2000 reports, of which 19 are listed for test substance-containing products.

- 13/19 skin reaction cases since 1987 with two formulations (both 500 g/L formulations)

- Most cases involve negligible or minor exposure, where symptoms are reported they are

classified as ‘minor’.

- 5 cases were consistent with allergic reaction though not necessarily to the test substance

- No patch-testing was carried out

- 1 case in 1994 involved a formulation plant worker who worked in the packing area (57% test substance)

-The HSE Medical Adviser suspected an anaphylactic reaction, but no further testing wascarried out

 

2. US FASTMED data
This is the US equivalent of the adverse incident database for the North American market and isnow operated through the Prosar corporation. The historical data transfer (from previousserviceprovider) to the new provider has not been completed so information is only readily availablefrom the beginning of June 1997.

Of the 7 reported cases, three are minor ocular irritation; two report wheezing, although one ofthese was a fire fighter attending a warehouse fire involving several pesticides; one case ofgeneral malaise but no details on exposure; and one case of skin contamination where theundiluted product was spilt on legs - person was asymptomatic.

 

3. UK National Poisons Information Service (London) Data

The Poisons Information service within the Medical Toxicology Unit of Guy’s and St. Thomas’NHS Trust is a 24 hour telephone service providing information to the medical profession on thetreatment and management of poisoned patients.

The data for 1995-1999 shows a total of 14 cases wherethe test substancewas thought to have beeninvolved. Of these only 4 were dermal exposures - one case was an accidental exposure of a childresulting in dermatitis and three cases of occupational exposure, each resulting in minor skinrashes. In none of the cases was it determined whether the effects were irritation or sensitisation.

 

4. California Pesticide Illness Surveillance

-133 case reports between 1982–1992

-There were 42 cases showing skin effects, 39 with eye effects and 3 with respiratory effects

-Few details are given, in most instances skin irritation and rash are mentioned. Allergiccontact dermatitis is referred to in a few cases, although it was considered unlikely by ISK’sMedical Adviser

-22 cases involved re-entry or accidental overspraying. In 10 cases contact dermatitis wasdiagnosed, 3 cases involved acute , urticaria-type reactions, and 1 case allergic asthma. ISKconsidered allergic reactions unlikely.

 

5. Published Literature

A search of the scientific literature for reports of human adverse incidents associated withthe test substanceidentified the following:

Author	No. of cases	Patch-test
Bach 1980	1	+ve at 0.01%test substance. Controls +ve at 0.1%
Spindeldreier 1980	3	+ve at 0.01%test substance. Controls -ve at 0.1%
Johnsson 1983	14	7/14 workers and 1/14 controls +ve at 0.01%test substance.
Bruynzeel 1986	3	2/3 workers +ve at 0.01% test substance. or aq. 4/17 controls had faint redness
Meding 1986	1	+ve at 0.0001% test substance. No controls
Liden 1990	1	0.0001% test substance in water +ve. 10 controls -ve

 

The ISK interpretation of these reports is that they do not confirm skin sensitisation and that persistent sub-clinical irritancy may have pre-disposed to contact irritation.

 

Author	No. of cases	Summary
Dannaker 1993	1	Contact urticaria with facial oedema and wheezing, open application of test substance-treated wood +ve, untreated wood -ve. Open application of 0.01% aq. test substance resulted in analphylactic reaction.
Huang 1995	28	Survey of test substance formulation workers found higher incidence of respiratory symptoms. Some LF parameters were abnormal. 2/28 workers tested +ve for test substance 0.05% petr
Penagos 1996	39	4/39 banana workers with erythema dyschromicum perstans (ashy dermatitis) tested positive for test substance 0.001% ac. compared to 0/41 controls.
Matsushita 1996	1	1 case study of male photoallergic contact dermatitis following exposure to formulation

 

In summary, there have been few reports in the literature of adverse responses in humans to the test substance. Most of the reported effects can be linked to the irritation potential of the technical material, although it must be noted that there was little work carried out to differentiate between irritation and sensitisation.

Although the absence of evidence of skin effects is not evidence of absence of effects, the test substance have been extensively used for over 30 years, in a variety of applications. If the skin sensitising potential was high, then a greater number of reports would been expected. Although the formulations with the test substance have the potential to cause skin sensitisation in humans, the data from over 30 years of practical use show that it is of low potency.