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Description of key information

Acute oral toxicity:


A dose of 25 mg/kg body weight was tolerated by male and female rats without mortalities, clinical signs, effects on weight development and gross pathological findings.
At 200 mg/kg in both sexes piloerection, constipation, decreased motility, decreased reactivity, labored breathing, and in females pallor and uncoordinated gait were observed. Additionally to the above described signs, at 2,000 mg/kg in females increased motility, increased salivation and in one animal abdominal position were observed. The signs observed occurred within 5 minutes after administration and lasted up to day 14 of the study. 200 mg/kg and 2,000 mg/kg were lethal. At 200 mg/kg two males and two females, and at 2,000 mg/kg two females died during the study.
The treatment induced a clear body weight depression on day 8 of the study at 200 mg/kg and above. The gross pathology investigations performed at the end of the post-treatment observation period showed pale discolorations on liver, thickened forestomach, pale discolorations on kidneys, and adhesions in the abdominal cavity, where liver, forestomach, spleen and abdominal wall were adhered.


 


Acute inhalation toxicity:


Three groups of rats were nose only exposed to a mean concentrations of 78, 144, 489, and 1975 mg test substance/m3 air.


Observations and Measurements: Vapor concentrations of 78 mg/m3 and above resulted in a concentration-dependent mortality occurring up to the first postexposure day and clinical signs, such as: bradypnea, labored breathing pattern, stridor, rales, dyspnea, serous discharge from nose, nostrils/muzzle with red discolorations and encrustations, periorbicular hyperemia/swelling, corneal opacity, forelimbs reddened, piloerection, ungroomed hair-coat, cyanosis, prostration (ventral position), apathy, motility reduced, reduced reflexes, limp, tremor, hypothermia, emaciation; and decreased body weights. The intensity and duration of clinical signs was governed by respiratory effects. Gross necropsy appears to suggest that mortality was causally related with acute lung edema.


In summary, the evaporated test substance proved to have a high acute inhalation toxicity to rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Feb- Mar 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
1996
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
Purity: 92.1 %
Identity/Stability in the vehicle confirmed analytically.
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
5 ml/ kg BW
Doses:
male: 25 and 200 mg/kg bw
female: 25, 200 and 2000 mg/kg bw
No. of animals per sex per dose:
5 anmials per sex and dose
Control animals:
no
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 50 - < 200 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 50 - < 200 mg/kg bw
Based on:
test mat.
Mortality:
At 200 mg/kg two males and two females, and at 2,000 mg/kg two females died during the study.
Clinical signs:
A dose of 25 mg/kg body weight was tolerated by male and female rats without
mortalities and clinical signs.
At 200 mg/kg in both sexes piloerection, constipation, decreased motility, decreased
reactivity, labored breathing, and in females pallor and uncoordinated gait were
observed. Additionally to the above described signs, at 2,000 mg/kg in females
increased motility, increased salivation and in one animal abdominal position (no.3)
were observed.
The signs observed occurred within 5 minutes after administration and lasted up to
day 14 of the study.
Body weight:
At 200 mg/kg and above a clear body weight depression was detected.
Gross pathology:
In animals that died during the observation period the following changes were
detected:
Liver: pale and dark-red discolorations; distinct tabulation;
Lung: slightly collapsed;
Spleen: pale discoloration;
Kidneys: pale discoloration;
Forestomach: thickened; adhesion to abdominal wall;
General observations: autolysis

Animals killed at the end of the study period showed the following changes:
Body cavity: adhesions of stomach (forestomach), and liver to abdominal wall
Liver: pale discoloration; adhesions to forestomach
Stomach: adhesions of forestomach to abdominal wall, forestomach thickened
Spleen: adhesions
Kidneys: pale discoloration















































Dose [mg/kg b.w.]



Toxicological results


 



Duration of signs



Time of death



Mortality


[%]



 



a)



b)



c)



males



 



 



25



0



0



3



-



-



0



200



2



3



3



5h        - 10d



3d        - 6d



67



 



 



 



 



females



 



 


































25



0



0



3



-



-



0



200



2



3



3



5h        - 13d



8d



67



2,000



2



3 -



3



5'        - 14d



2d



67




  1. number of dead animals

  2. number of animals with signs

  3. number of animals in the group

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
LD50: >50 <200 mg/kg body weight
Executive summary:

A study for acute oral toxicity in male and female Wistar rats was conducted with the test substance JAU 6476 - Chloromethylketone.
The method used complied with the OECD - Guideline for Testing of Chemicals No. 423.


A dose of 25 mg/kg body weight was tolerated by male and female rats without mortalities, clinical signs, effects on weight development and gross pathological findings.
At 200 mg/kg in both sexes piloerection, constipation, decreased motility, decreased reactivity, labored breathing, and in females pallor and uncoordinated gait were observed. Additionally to the above described signs, at 2000 mg/kg in females increased motility, increased salivation and in one animal abdominal position were observed. The signs observed occurred within 5 minutes after administration and lasted up to day 14 of the study. 200 mg/kg and 2000 mg/kg were lethal. At 200 mg/kg two males and two females, and at 2000 mg/kg two females died during the study.
The treatment induced a clear body weight depression on day 8 of the study at 200 mg/kg and above. The gross pathology investigations performed at the end of the post-treatment observation period showed pale discolorations on liver, thickened forestomach, pale discolorations on kidneys, and adhesions in the abdominal cavity, where liver, forestomach, spleen and abdominal wall were adhered.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
50 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Jan - Feb 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
adopted 12 May 1981
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: EG Guideline 92/69/EWG. Journal of the European Community - Legal Specifications L 2383 A, 35.
Version / remarks:
29 December 1992
Qualifier:
according to guideline
Guideline:
other: OPPTS 870.1300 (1998). US-EPA Health Effects Test Guidelines 870.1300 - Acute Inhalation Toxicity. United States Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances, EPA 712C-98-193
Version / remarks:
1998
GLP compliance:
yes
Test type:
traditional method
Limit test:
no
Specific details on test material used for the study:
Purity 92.1%
Species:
rat
Strain:
Wistar
Remarks:
Hsd Win:WU
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 2 - 3 months
- At the study start the variation of individual weights did not exceed ±10 per cent of the mean for each sex
- Housing: individually in Makrolon cages type II during the acclimation and study periods
- Diet: Altromin® 1324 diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2.0
- Humidity (%): approximately 50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Plexiglas exposure tubes (TSE, Bad Homburg, Germany)
- Exposure chamber volume: 3.8 L (dimensions of the inhalation chamber: inner diameter =14 cm, outer diameter = 35 cm (two-chamber system), height = 25 cm)

- Source and rate of air: compressed air supplied by Boge compressors
- Method of conditioning air: automatically by a VIA compressed air dryer
-Vapor generation: Under dynamic conditions the test substance was evaporated
from a glass flask from which the substance was conveyed into the intake of the
cylindrical inhalation chamber. The test substance was contained in a bubbler (glass
flask {filling height: «5-7 cm, diameter: »5 cm} filled with approximately 140 g was
equilibrated at 30 °C. Specified flows of dry air (see Table 1, result section) were fed
through the bubbler and diluted with additional air. The total air flow through the
chamber was 15 L/min;
- controlled temperature and humidity measurements

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric analysis with cellulose-acetate filter
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
nominal: 78, 144, 489 and 1975 mg/m3 ;
analytical: 52.1, 90.1, 413.5, 1749.3 mg/m3
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs: several times on the day of exposure and at least once daily thereafter; body weights: measured prior to exposure and on Day 3 and 7 and weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Statistics:
Necropsy findings: If specific findings occur from the respiratory tract of surviving rats they are evaluated statistically using the pair-wise Fisher test after the R x C chisquared test. For calculation of the unilateral p value a symmetrical distribution was assumed (p unilateral = (p bilateral)/2).

Since in acute studies individual group means may differ prior to commencement of the first exposure, the body weight gain was statistically evaluated for each group. For these evaluations a one-way ANOVA (vide infra) is used.

Physiological data: Data of rectal temperature measurements are statistically evaluated using the ANOVA procedure (vide infra).

Calculation of the LC50: If calculation of a median lethal concentration (LCso) is possible, it is performed by computer (PC) according to the method of Rosiello et al. (1977) as modified by Pauluhn (1983). This method is based on the maximum likelihood method of Bliss (1938). If only 2 pairs of values with greater than 0% lethality and less than 100% are available then the first linear approximation is based on these values and a x2-homogeneity test is not performed. In this case the interpolated concentration at 50% lethality is designated the approximate LD50. Additionally, the moving average interpolation according to Schaper et al. (1994) is used for calculation, if applicable.

Analysis of variance (ANOVA): This parametric method checks for normal distribution of data by comparing the median and mean.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
124 mg/m³ air
Based on:
test mat.
95% CL:
82 - 185
Exp. duration:
4 h
Mortality:
Mortality occurred at all exposure levels tested. Rats succumbed on the exposure
day up to the first postexposure day.
LC50 (males and females combined): 124 mg/m3 air
Confidence interval (95%): 82-185 mg/m3
Clinical signs:
other: Details concerning signs and observations are provided in the Appendix in the form of various incidence tables. The following list of signs is focusing on toxicologically significant signs only. Group 1: All rats tolerated the exposure without specific si
Body weight:
Results of the evaluation of the body weights are included in the Appendix.
Comparisons between control animals with the groups exposed to the test substance
revealed transient, statistically significant effect on body weights.
Gross pathology:
Effects on organs: Animals succumbed during the exposure or post-observation period: Lung less collapsed, with dark-red foci/areas, serous foamy content in trachea, hydrothorax, clear to red
discharge from nose.

Animals sacrificed at the end of the post-observation period: In rats exposed to the test compound a conclusive, increased incidence of macroscopic findings were not observed.

Gross necropsy appears to suggest that mortality was causally related with acute lung edema
Other findings:
Results of the evaluation of the rectal (colonic) temperature are summarized in the
Appendix. Statistical comparisons between control animals with the groups exposed to the test substance revealed a conspicuous hypothermia.

Table 2: Summary of acute inhalation toxicity - 4 hour exposure to evaporated test
substance













































































































NTarget Onset and Rectal
GroupConcentrationToxicologicalDuration ofOccurrenceTemperature
/sex(mg/m3)ResultSignsof Mortality(°C)
1 /m00 / 0 / 537.5
2/m750 / 5 / 5Od-10d31.9**
3 /m1504 / 5 / 5Od-10d1d28.6**
4 /m5005 / 5 / 5Od-1d1d27.5**
5 /m20005 / 2a / 5OdOd, 1d24.7**
1/f00 / 0 / 5~38.2
2 / f751 / 5 / 5Od-7d1d32.6**
3 / f1502 / 5 / 5Od - 14d1d30.1**
4/f5005 / 4 / 5Od-1dOd,1d27.7**
5 / f20005 / 4 / 5OdOd, 1d25.9**

N = group assignment, m = males, f = females; a) any number smaller than 5 means that animals
succumbed during the exposure period, Od: exposure day, ** p < 0.05
Values given in the Toxicological results' column are:
1st = number of dead animals.
2nd = number of animals with signs after cessation of exposure.
3rd = number of animals exposed.

Interpretation of results:
Category 1 based on GHS criteria
Conclusions:
LC50 inhalation (vapor, 4 hr) = 124 mg/m3 (0.124 mg/l) air;
Confidence interval (95%): 82-185 mg/m3 air
Executive summary:

A study on the acute inhalation toxicity of 1-Chloro-1-chloroacetylcyclopropane (hereafter referred to as test substance) on rats has been conducted in accordance with OECD Guideline No. 403. Test procedures were adapted so as to comply also with the Directive 92/69/EEC and OPPTS 870.1300. Three groups of rats were nose only exposed to a mean concentrations of 78, 144, 489, and 1975 mg test substance/m3 air.


Observations and Measurements: Vapor concentrations of 78 mg/m3 and above resulted in a concentration-dependent mortality occurring up to the first postexposure day and clinical signs, such as: bradypnea, labored breathing pattern, stridor, rales, dyspnea, serous discharge from nose, nostrils/muzzle with red discolorations and encrustations, periorbicular hyperemia/swelling, corneal opacity, forelimbs reddened, piloerection, ungroomed hair-coat, cyanosis, prostration (ventral position), apathy, motility reduced, reduced reflexes, limp, tremor, hypothermia, emaciation; and decreased body weights. The intensity and duration of clinical signs was governed by respiratory effects. Gross necropsy appears to suggest that mortality was causally related with acute lung edema.


In summary, the evaporated test substance proved to have a high acute inhalation toxicity to rats.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
124 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the study results for acute toxicity allocation to category 3 for oral toxicity (H301) and category 1 for inhalative toxicity (H330) according to Regulation (EC) No. 1272/2008 (CLP), ANNEX I, is warranted.