1-chloro-4-[(prop-2-yn-1-yloxy)methyl]benzene

Endpoint summary

Description of key information

An acute oral LD50 was determined to be in the range of > 300 to < 500 mg/kg bw in rats. 
An acute dermal LD50 was determinde to be > 2000 mg/kg bw in 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:

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

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

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

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

300 mg/kg bw

Quality of whole database:

Experimental study according to guideline and GLP.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014-12-16 to 2015-02-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Experimental study according to guideline and GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

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:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Age at study initiation: male: approx. 8 weeks, female: approx. 12 weeks
- Weight at study initiation: Animals of comparable weight (± 20 % of the mean weight)
- Fasting period before study: no
- Housing: single, Makrolon cage, type III
- Diet: at libitum, VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, with bedding (H 15005-29; Ssniff, Spezialitäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany))
- 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

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal and dorsolateral parts of the trunk
- % coverage: About 40 cm² (corresponds to at least 10 % of the body surface)
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing: warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 1.77 mL/kg bw
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Scoring: 30-60 min after removal, weekly and on last day of observation period
- Frequency of observations and weighing: Observations: several times on first day, afterwards at least once per day; weighing: shortly before application, weekly and on last day of the observation period
- 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.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

No systemic clinical signs were observed. No local effects were observed.

Body weight:

Body weight of male animals increased within normal range.
One female showed a loss of body weight. Two females showed a stagnation of body weight in the first week but otherwise the increase was normal. One female showed a constant stagnation during the complete observation period. Due to the fact that stagnation or slight loss of body weight is commonly known for females dermally applied and the affected animals neither showed any clinical symptoms nor change in behavior these findings are considered to be unspecific.

Gross pathology:

No macroscopic pathologic abnormalities were observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Experimental study according to guideline and GLP.

Additional information

Acute toxicity

Oral

An acute oral toxicity study with the test substance was conducted in rats according to OECD TG 423. Female animals received 500 mg/kg bw (3) or 300 mg/kg bw (6) one time via gavage and were observed for 14 days. All animals of the 500 mg/kg bw treatment group died within the first two days. From the 300 mg/kg bw treatment group one animal died within the first two days while the other animals survived the observation period. Animals that died showed a reduced body weight after death while the surviving animals showed a body weight development within the normal range and expectation of the animals development status. All animals presented with an impaired general state and piloerection. Those clinical signs lasted up to three days in the survivors and were not detected afterwards. Gross pathology of the survivors showed no macroscopic changes. Animals that died showed congestion of the kidneys, light and dark spots on the liver, liver light red with dark spots, red discoloration of the fully-filled stomach, red discoloration of the glandular stomach, red discoloration of the small intestine with red discolored contents and red discoloration of the urinary bladder contents. Due to those observations the acute oral LD50 was determined to be in the range of > 300 < 500 mg/kg bw in rats. Therefore the test substance is considered to be classified for acute oral toxicity in Category 4 according to CLP. 

 

Dermal

An acute dermal toxicity study in rats was performed according to OECD TG 402. The limit test was conducted with a semiocclusive application of 2000 mg/kg bw on clipped skin. The test substance was applied for 24 h and removed afterwards. The animals were observed for 14 days. No clinical signs were detected. All male and two female animals showed a development of body weight that was within the normal range of weight gain. Three females showed stagnation/loss of bodyweight which was, due to a lack of alterations in behavior and clinical signs, explained as a commonly observed effect after dermal application to female rats. Pathology showed no abnormalities in all animals. Therefore the acute dermal LD50 of the test substance was determined to be > 2000 mg/kg bw in rats.

Justification for selection of acute toxicity – oral endpoint
The study is considered reliable.

Justification for selection of acute toxicity – dermal endpoint
The study is considered reliable.

Justification for classification or non-classification

Acute oral toxicity

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008, as amended for the seventh time in Regulation (EC) No 2015/1221. As a result the substance is considered to be classified for acute oral toxicity in Category 4. H302: Harmful if swallowed

 

Acute dermal toxicity

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008, as amended for the seventh time in Regulation (EC) No 2015/1221. As a result the substance is considered to be not classified for acute dermal toxicity.