Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Comparable to guideline reliable with restrictions - The stability of the test substance was not stated. - In the report it was stated that the study was conducted according to OECD 401 (1987) and OECD 423 (1996). Looking at the study it seemed to correspond the most with OECD 423 (1996) and the study was compared to this guideline. - According to the guideline OECD 423 (1996) when 2-3 animals of one sex died at the dose level of 200 mg/kg the next lower dose should be tested. If only 1 or none of the animals died the same dose level is test in the next sex. In this study 4 out of 5 females died, which means the next lower dose level should have been tested, but in this study the males were also tested. At the dose level of 200 mg/kg only one male died. Then a lower dose (50 mg/kg) was tested with the females and all females survived. The males were not tested at this dose level. This is considered to be justified since the results of the 200 mg/kg dose level indicated that the females were the most sensitive sex and literature surveys of conventional LD50 tests show that usually there is little difference in sensitivity between sexes, but those cases were differences are observed, females are generally slightly more sensitive. - According to the guideline, three animals of one sex are used for each step. At the 200 mg/kg dose level more than three animals were used of one sex and at the 50 mg/kg dose level 5 females were used for testing.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 1996-03-22
Deviations:
yes
Remarks:
- According to the guideline, individual animal data should be summarized in tabular form. The data for clinical observations and necropsy were only provided in narrative form and not in tabular form.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
, adopted 1987-02-24
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Zinc selenite
- Substance type: technical product
- Physical state: solid, white powder
- Storage condition of test material: ambient temperatures
- Density: 2 kg/l

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, Germany
- Age at study initiation: 7 to 10 weeks old
- Weight at study initiation: mean body weight for females: 173.5 g (2000 mg/kg dose level); 170 g ( 200 mg/kg dose level); 168 g (50 mg/kg dose level); mean body weight for males: 212 g (500 mg/kg) and 232 g (200 mg/kg dose level)
- Fasting period before study: Prior to dosing, the animals had fasted overnight. Approximately four hours after dosing, they had access to food again.
- Housing: Five animals per cage (stainless steel cages, fitted with wire-screen floor and front)
- Diet (ad libitum): Standard laboratory rodent diet (Supplier. SDS Special Diets services, Whitham, England)
- Water (ad libitum): tap water (N.V. Waterleidingbedrijf Midden-Nederland)
- Acclimation period: 13, 16, 21, 23 or 27 days depending on dose group

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3 °C
- Humidity: 62.5 - 90 % (upper limit higher than 70 % because meteorological circumstances and/or wet cleaning of the animal room; the 90 % peak occurred for some hours at most)
- Ventilation: ca. 10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 /12
No further information on the test animals was stated.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
maize oil
Details on oral exposure:
A first screening was carried out with two females treated with a dose level of 2000 mg/kg body weight to check for mortality. Since these animals did not survive, the study was continued with 2 males dosed with the next lower dose level of 500 mg/kg belonging to EPA-classification. These animals also did not survive and subsequently two females were dosed with the next lower dose level of 200 mg/kg belonging to EC-classification. Since these two animals survived the first two days it was decided to complete this dose level with three females and five males. After completion of this dose level it appeared that one male and four females did not survive. Therefore, it was decided to dose an additional five females with the next lower dose level of 50 mg/kg dose level belonging to EPA-classification. The 50, 200, 500 and 2000 mg/kg dose levels were applied to the animals as a 5, 20, 50 and 200 mg/ml suspension in maize oil, respectively. In each case the dosing -volume was 10 ml/kg body weight. The exact amount of the test substance to be dosed was calculated for each animal individually and administered by means of a syringe, equipped with an oral gavage.
No further information on the oral exposure was stated.



Doses:
50, 200, 500, 2000 mg/kg body weight
No. of animals per sex per dose:
2000 mg/kg: 2 females
500 mg/kg: 2 males
200 mg/kg: 5 females / 5 males
50 mg/kg.: females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for clinical symptoms were made within 1 hour and within 4 hours after dosing, and subsequently at least once daily throughout an observation period of 14 days. The body weights of each animal was recorded immediately before dosing on day 0 and, if surviving, on days 3, 7 and 14 of the study. In addition, the body weight of animals which intercurrently died were recorded when found dead.
- Necropsy of survivors performed: Yes
At the end of the observation period, on day 14 of the study, all surviving animals were killed with carbon dioxide and examined for external changes. Next, the abdomen and the thorax of each animal was opened and examined for gross pathological changes. The animals found dead or killed in extremis were also examined for gross pathological changes.
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: For clinical symptoms all visible reactions to treatment were recorded, including type, severity, onset and duration.
No further information on the study design was stated.
Statistics:
No data

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
200 - 500 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
50 - 200 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 50 - <= 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: On the basis of the mortality observed, the oral LD50 of zinc selenite is considered to be between 50 and 500 mg/kg bw (200 and 500 mg/kg bw for males and between 50 and 200 mg/kg bw for females).
Mortality:
2000 mg/kg dose level (in 2 females):
Two days after dosing one female was found dead, while the other female was found in a moribund condition. Therefore, it was decided to kill this animal for humane reasons.
500 mg/kg dose level (in 2 males):
Three days after dosing one male was found dead, while five days after dosing the other male was found in a moribund condition. therefore, it was decided to kill this animal for humane reasons.
200 mg/kg dose level (in 5 males and 5 females):
One male was found dead on day 1 after dosing; one female on days 2 after dosing; two females on day 3 after dosing. Four days after dosing one female still showed emaciation, sluggishness, soiled fur and diarrhoea. Since the next day these signs (and additionally tremors) were still present, it was decided to kill this animal for humane reasons.
50 mg/kg dose level (in 5 females):
All five females survived treatment with the 50 mg/kg dose level.
Clinical signs:
2000 mg/kg dose level (in 2 females):
- Sluggishness: At 24 hours after dosing in both females. At 48 hours after dosing in one female.
- Piloerection: At 4 hours after dosing in both females. At 48 hours after dosing in one female.
- Soiled fur: At 48 hours after dosing in one female.
- Pallor: At 24 hours after dosing in one female. At 48 hours after dosing in the other female.
- Blepharospasm: At 24 hours after dosing in both females. At 48 hours after dosing in one female.
500 mg/kg dose level (in 2 males):
- Sluggishness: At 4 and 24 hours after dosing in both males.
- Piloerection: At 4 - 48 hours after dosing in both males.
- Diarrhoea: At 1-24 hours after dosing in both males.
- Soiled fur and weakness: On days 4 and 5 after dosing in one male.
200 mg/kg dose level (in 5 males and 5 females):
- Sluggishness: At 1 -48 hours after dosing in three females. At 48 and 72 hours after dosing in one of the other females. At 4 hours after dosing in all males and at 24 hours after dosing in three males.
- Encrustation nose: At 24 hours after dosing in two females. At 48 hours after dosing still in one of the two females.
- Piloerection: At 1 hour after dosing in two females and at 4 hours after dosing in all females. At 4 hours after dosing in all males and at 24 hours after dosing in four males.
- Diarrhoea: At 1 -72 hours after dosing in one female. At 1- 24 hours after dosing in another female. At 4 and 24 hours after dosing in the remaining females.
- Soiled fur: At 24 -72 hours after dosing in 4 males and in one female. At 24 hours after dosing in remaining four females.
50 mg/kg dose level (in 5 females):
- Piloerection: At 4 hours after dosing in all females.
- Diarrhoea: At 4 and 24 hours after dosing in all females.
- Soiled fur: At 24 and 48 hours after dosing in three females.

Body weight:
2000 and 500 mg/kg dose levels:
Not determined since all animals treated with these dose levels died or were killed in a moribund condition.
200 mg/kg dose level:
Apart from a dip in body weight of one female and three males the surviving animals gained weight during the 14-day observation period.
50 mg/kg dose level:
Apart from a dip in body weight in three females, the animals gained weight during the 14 day observation period.
Gross pathology:
2000 mg/kg dose level:
Stomach filled with air and whitish content in both females.
500 mg/kg dose level:
Stomach filled with air and whitish areas in one male.
200 mg/kg dose level:
Inflammation of the stomach and firm remains of ingested food in three females and pale adrenals in one male.
50 mg/kg dose level:
Examination of the 5 females at autopsy did not reveal treatment-related gross alterations.

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
On the basis of the mortality observed, the oral LD50 of zinc selenite is considered to be between 50 and 500 mg/kg bw (200 and 500 mg/kg bw for males and between 50 and 200 mg/kg bw for females). According to 67/548/EC and subsequent regulations, zinc selenite requires classification as "toxic if swallowed". According to the EC Regulation No. 1272/2008 and subsequent regulations, zinc selenite requires classification as "Acute toxicity, oral, category 3" (Toxic if swallowed).