Registration Dossier

 Oral:
In a 13 week rat study species-specific kidney toxicity [alpha-2µ-microglubulin nephropathy]) was reported at 300 mg/kg bw/day. For effects other than kidney toxicity the NOAEL in males and females was 600 mg/kg bw /day (NTP 1987).
In a 52 week study with beagle dogs the relative and absolute organ weights (adrenal gland, thyroid gland) were increased in both sexes at >= 50 mg/kg/bw without histopathological changes. Together with the observed changes in liver and kidneys the overall NOAEL in that study is 10 mg/kg bw/day (Naylor 1996).
Thus, the lower NOAEL of 10 mg/kg bw/day was determined in a one year oral dog study. This NOAEL has to be considered in the risk characterisation of p-dichlorobenzene because there is no evidence that this specie with the higher sensitivity for p-dichlorobenzene exposure is a less appropriate model for humans than rodents (EU RAR, 2004). Therefore, the NOAEL of 10 mg/kg bw/day will be taken as starting point for the derivation of the systemic, oral, longterm DNEL for worker and consumer.
Inhalation
In a repeated dose inhalation toxicity study in rats (2 years) the NOAEC was 75 ppm for systemic effects in liver and kidney (Centrilobular hypertrophy of hepatocytes and papillary mineralization and pelvic urothelial hyperplasia of the kidney were noted in the 300 ppm-exposed rats) as well as local effects at the respiratory tract (AISO 2005).
 Dermal: 
There are no valid data available

Reference

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No OECD guideline defined.

Principles of method if other than guideline:

Repeated dose toxicity study: p-dichlorobenzene was applied to dogs in gelatine capsules once per day, 5 days per week for 52 weeks

GLP compliance:

yes

Limit test:

no

Species:

dog

Strain:

Beagle

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation: 7 months
- Weight at study initiation: males: 6.8-11.4 kg; females 6.9-11.1 kg
- Fasting period before study:
- Housing: individual
- Diet ad libitum
- Water ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
details not provided
animal housing ans husbandry in accordance witht he provisions of
" guide to the care and use of laboratory animals"
USPHS-NIH publication No. 86-23

Route of administration:

oral: capsule

Vehicle:

other: Gelatin Capsule

Details on oral exposure:

p-dichlorobenzene was applied in gelatine capsules once per day, 5 days per week

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

1 year

Frequency of treatment:

once per day, 5 days/week, 52 weeks

Remarks:

Doses / Concentrations:
0, 10, 50, 150/100/75 mg/kg bw/day
Basis:

No. of animals per sex per dose:

5/sex/dose

Control animals:

yes

Details on study design:

in a one-year oral toxicity studc p-dichlorobenzene was administered to Beagle dogs byy capsule once per day , at dose levels of 0, 10, 50, 150 mg/kg bw/day. The highest dose was reduced at first to 100 and then to 75 mg/kg bw/day due to exessive toxicity.. treatment was determined after one year and animals were subjected to detailed examination

Positive control:

no

Observations and examinations performed and frequency:

daily observations, body weight determination once per week, food consumption ophthalmoscopic examination, hematology ,. clinical chemistry , urinalysis

Sacrifice and pathology:

all animals that died and those sacrificed on shedul were subjected to gross pathological examination: organ weights andhistopathological examination

Other examinations:

no

Statistics:

e. g.: Dunnett's multiple comparison test, decision-tree anlysis, Fisher's exact test, Grubb's test

Clinical signs: