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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2014-12-16 to 2015-03-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Experimental study according to guideline and GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Bioassay Labor für biologische Analytik GmbH, 69120 Heidelberg
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1-chloro-4-[(prop-2-yn-1-yloxy)methyl]benzene
EC Number:
813-130-5
Cas Number:
4039-86-5
Molecular formula:
C10H9ClO
IUPAC Name:
1-chloro-4-[(prop-2-yn-1-yloxy)methyl]benzene

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: 168-185 g
- Fasting period before study: at least 16 h, water was available
- Housing: single, Makrolon cage, type III
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, with bedding (H 15005-29; Ssniff, Spezialitäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany)) and enrichment (Wooden gnawing blocks (Type NGM E-022) ; ABEDD® LAB & VET Service GmbH, Hasnerstraße 84/6; 1160 Wien – Austria)
- Water: ad libitum, tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/ 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 3 and 5 g/100 mL
- Amount of vehicle: 10 mL/kg bw
- Justification for choice of vehicle: The OECD guideline states that an aqueous formulation is recommended where ever possible. Therefore a 1 % solution of CMC in deionized water was applied as a good homogeneity in water could not be guaranteed.
- Source: sodium carboxymethylcellulose, Dow Wolff Cellulosics GmbH

CLASS METHOD
- Rationale for the selection of the starting dose: By request of the sponsor a starting dose of 300 mg/kg bw was administered to 3 female rats in the first step. Because no mortality occurred, 500 mg/kg bw were administered to another group of 3 female animals in the second step. As all animals died in this step, 300 mg/kg bw were administered to another group of 3 female animals in the third step. As in this step only one animal died, the study was terminated.
Doses:
300 and 500 mg/kg bw
No. of animals per sex per dose:
3 for 500 mg/kg bw, 6 for 300 mg/kg bw in two groups
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter. Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation and on the day of death starting.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Calculations were performed using Microsoft Excel 2003 and checked with a calculator.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 500 mg/kg bw
Based on:
test mat.
Mortality:
500 mg/kg bw: all 3 animals dead on day 2
300 mg/kg bw: no mortality in first test group, 1 animal dead on day 2 in second group
Clinical signs:
500 mg/kg bw: impaired general state, piloerection and cowering position (starting 1 h after administration, on day 1)
300 mg/kg bw: impaired general state, piloerection from 1 h after treatment up to 3 days. One animal that died showed dyspnea and staggering.
Body weight:
500 mg/kg bw: Animals showed a reduced body weight after death.
300 mg/kg bw: Animals showed a normal increase in body weight during the study period. The animal that died showed a reduced weight after death. One animal lost weight during the second week of treatment (most probably due to normal slow growth in the age range).
Gross pathology:
500 mg/kg bw: Animals showed congestion of the kidneys, liver light red with dark spots, red discoloration of the fully-filled stomach, red discoloration of the small intestine with red discolored contents and red discoloration of the urinary bladder contents.
300 mg/kg bw: The animal that died showed congestion of the kidneys, light and dark spots on the liver, red discoloration of the glandular stomach and red discoloration of the small intestine with red discolored contents. Animals that were killed after the observation period showed no macroscopic changes.

Applicant's summary and conclusion