Flue dust, portland cement

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07.04.2010 to 06.05.2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study, according to the OECD 422 technical guideline

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 422

Deviations:

no

GLP compliance:

yes

Test type:

other: Repeated dose toxicity

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Flue dust, portland cement

EC Number:

270-659-9

EC Name:

Flue dust, portland cement

Cas Number:

68475-76-3

Molecular formula:

It is a UVCB.

IUPAC Name:

Flue dust from Portland cement clinker production

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Wistar outbred rats were obtained from a colony maintained under SPF conditions from Charles River Wiga GmbH, Sulzfeld, Germany. Upon arrival, the rats were quarantined (animal room 05.1.11, DRF and main study) and checked for overt signs of ill health and abnormalities. During the quarantine period serological examinations of the microbiological status of the rats were conducted in a random sample. After 5 days (DRF) and 2 days (main study) the results of serology appeared to be satisfactory and the animal room was cleared for use as experimental room. The animals were acclimatized to the laboratory conditions for 6 days. One day before the first exposure (day -1 of the study) on 15 March 2010 (DRF) and 5 April 2010 (main study), the animals (males and females separately) were allocated to the various groups by computer randomization proportionately to body weight. Surplus animals were kept in the animal room for monitoring during the study. They were sacrificed at the end of the in-life segment of the study.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Details on oral exposure:

The test item was administered to the animals in the diet. This route of administration was chosen because this is a likely route of human exposure under the specific conditions of its use.
Dose-range finding study
The test item was administered to all rats at constant concentrations in the diet for 1 week.
Main study
The test item was administered to all rats at constant concentrations in the diet for approx. 2 weeks
prior to mating, during mating, gestation and lactation up to day 4 or shortly thereafter. Male animals were exposed for 30 days

Doses:

Dose-range finding study: up to 20000 mg/kg diet = up to 1848 mg flue dust / kg bw/ day
Main study: up to 16000 mg/kg diet = up to 1340 mg flue dust / kg bw/ day

No. of animals per sex per dose:

4 in the dose-range finding study and
12 in the main study

Control animals:

yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 848 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 value from a repeated dose toxicity test, no mortalities have been observed.

Mortality:

No mortalities occured during the study.

Clinical signs:

other: One male of the mid-dose group (5,000 mg/kg diet) showed soft faeces on day 3 of the study. No other clinical observations were detected.

Gross pathology:

Gross examination at necropsy revealed no exposure-related findings. The observed changes occurred in only one animal and are common gross findings in rats of this strain and age.

Any other information on results incl. tables

Dose-range finding study

Mortalities and clinical signs

No mortalities occurred during the study. One male of the mid-dose group (5,000 mg/kg diet) showed soft faeces on day 3 of the study. No other clinical observations were detected.

Body weight and body weight change

No statistically significant differences were observed in the mean body weight and body weight change of the male animals during this 1-week study. No differences in mean body weight were observed in the female animals. Body weight change of the female animals of the low-dose group (2,500 mg/kg diet) was statistically significantly increased; this was considered to be an incidental effect. Body weight change of the female animals of the top-dose group (20,000 mg/kg diet) was statistically significantly decreased between day 3-7 of the study.

Food consumption

Food consumption is expressed as g/animal/day or g/kg bodyweight/day. No statistically significant differences were observed in the food consumption of the male and female animals during the entire study.

Substance intake

Mean substance intake mg Flue dust T (REACH)/ kg body weight/ day

Group       B -       C -       D -        E

mg/kg diet 2,500 5,000 10,000 20,000

Males       172 337 695 1355

Females    235 419 914 1848.

Parental necropsy observations

Gross examination at necropsy revealed no exposure-related findings (Table 5). The observed changes occurred in only one animal and are common gross findings in rats of this strain and age.

Conclusion dose-range finding study Parental necropsy observations

The effects in the female animals on body weight were considered to be a treatment-related effect. No other treatment-related effects were observed. Considering the duration of the main study, at least 28 days for males and approx. 6-7 weeks for females, the following dose levels were chosen for the main study: 0 (control), 2,000 (low-dose), 6,000 (mid-dose) and 16,000 (high-dose) mg Flue dust T (REACH)/kg diet. It was intended that the mean substance intake in the high-dose group was comparable to approx. 1 g Flue dust T (REACH)/kg body weight/day.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Since all animals survived the highest dose level of 1848 mg/kg bw/d over a period of 7 days - and not as usal in a acute toxicity study for a single dose - , the oral LD50 of Flue Dust T (REACH) is considered to be higher than 1848 mg/kg body weight.

Executive summary:

Preceding the main study, Flue dust T (REACH) was studied in a 1-week dose-range finding study at dose levels of 0, 2,500, 5,000, 10,0000 or 20,000 mg Flue dust T (REACH)/kg diet. Body weight change of the female animals of the top-dose group (20,000 mg/kg diet) was statistically significantly decreased between day 3-7 of the study. No other treatment-related effects were observed. Considering the duration of the main study, at least 28 days for males and approx. 6-7 weeks for females, the following dose levels were chosen for the main study: 0 (control), 2,000 (low-dose), 6,000 (mid-dose) and 16,000 (high-dose) mg Flue dust T (REACH)/kg diet. It was intended that the mean substance intake in the high-dose group was comparable to approx. 1 g Flue dust T (REACH)/kg body weight/day.

No mortalities were observed in the main and in the dose range find study.