Hydrocarbons, C9, aromatics

Endpoint summary

Description of key information

Hydrocarbons, C9 Aromatics:

 

Acute Oral LD₅₀ = 3492 mg/Kg in rats (OECD TG 401)

Acute Dermal LD₅₀ >3160 mg/Kg bw in rabbits (OECD TG 402)

Acute Inhalation LC₅₀ >maximal attainable vapor concentration in rats (OECD TG 403)

 

Hydrocarbons, C10 Aromatics, >1% Naphthalene:

Acute Oral LD50 = 6318 mg/Kg in rats (OECD TG 401)

Acute Dermal LD50 >2000 mg/Kg in rabbits (OECD TG 402)

Acute Inhalation LC50 >4688 mg/m3 (OECD TG 403)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

From November 14, 1994 To January 5, 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report in agreement with OECD guideline 401-GLP

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

other: Crl:CDBR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Inc
- Age at study initiation: Males: Approximately 8-10 weeks; Females: Approximately 9-12 weeks
- Fasting period before study: Approximately 16 hours
- Weight at study initiation: Males: 217 to 317 grams; Females: 185 to 273 grams
- Housing: Individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:7-22days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): maintained range 20-24.4
- Humidity (%): maintained range 40-70
- Photoperiod (hrs dark / hrs light): 12hrs dark / 12 hrs light


IN-LIFE DATES: From: November 16, 1994 To: January 5, 1995

Route of administration:

other: oral intubation via syringe

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

No data

Doses:

5000mg/kg; 6000mg/kg; 7500 mg/kg; 10000 mg/kg

No. of animals per sex per dose:

10 animals per dose (5 male; 5 female)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were made as to the nature, onset, severity, and duration of toxicological signs at 1, 2, 4, and 6 hours after dosing, and once per day thereafter for a total of 14 Days. Body weights were recorded on the day prior to dosing (pretest), the day of dosing (Day 0), on Day 7, and on Day 14, and at death for those which succumbed.
- Necropsy of survivors performed: yes

Statistics:

The means and standard deviations of the body weights and body weight changes, by sex and group were calculated .

The oral median lethal dose (LD50) was calculated using the standard Litchfield-Wilcoxon technique (Litchfield and Wilcoxon, 1949) with equal weighting of the data values. If the fraction surviving was zero, the value was transformed to 1-(1/4n). If the fraction surviving was 1, it was transformed to the 1/4n, where 'n' is the number of animals in the dose group. The regression line was fitted by the least squares technique, using probit on log dose values.

The Litchfield-Wilcoxon recommended test for "goodness of fit" was performed. The significance level (probability) of the lack of fit test was calculated . If the probability is >0.05, the standard Litchfield-Wilcoxon technique was used to generate the confidence intervals for the slope and LD50. If the probability is 0.05 or less, then the modified Litchfield-Wilcoxon technique was used for calculating the confidence intervals.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 7 093 mg/kg bw

95% CL:

> 6 142 - < 8 190

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 5 558 mg/kg bw

95% CL:

> 4 592 - < 6 726

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 6 318 mg/kg bw

95% CL:

> 5 668 - < 7 044

Mortality:

5000 mg/kg: 0 males; 2 females
6000 mg/kg: 2 males; 3 females
7500mg/kg: 3 males; 5 females
10000 mg/kg: 5 males; 5 females

Clinical signs:

other: Adverse clinical effects were observed in all groups and were observed primarily during the first week of the study. Abnormal clinical signs noted during the study included hypoactivity; hypothermia; abnormal stool production; oral, nasal, and ocular dis

Gross pathology:

All animals which survived to study termination were free of abnormalities at postmortem examination (seven animals at the 5000 mg/kg dose level, five at the 6000 mg/kg dose level, and 2 at the 7500 mg/kg dose level), with the exception of one 5000 mg/kg male with alopecia.

Postmortem observations noted in the animals which died prior to scheduled termination examination included: staining of the fur; discolored kidneys, stomach and liver; and/or abnormal contents, discoloration or distention of the gastrointestinal tract or urinary bladder. These findings were considered to be treatment-related.

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LD50 for MRD-94-953 following oral intubation of (MRD-94-953) was established at 7093 mg/kg for males, 5558 mg/kg for females, and 6318 mg/kg combined. Classification is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Executive summary:

The acute oral toxicity and LD₅₀ of MRD-94-953 administered via oral intubation were evaluated in Crl:CDBR rats.  The dose levels were 5000, 6000, 7500, and 10000 mg/kg.  Each dose group consisted of 5 animals/sex.  Animals were observed daily for 14 days post dosing.  Overt signs of toxicity were apparent at a dose level of 5000 mg/kg and higher.  Mortality was observed at all dose levels tested and all of the animals that succumbed following administration of MRD-94-953 died within 3 days of dosing.  The incidence of death was considered dose related.  All animals which survived to study termination were free of abnormalities at postmortem examination (seven animals at the 5000 mg/kg dose level, five at the 6000 mg/kg dose level, and 2 at the 7500 mg/kg dose level), with the exception of one 5000 mg/kg male with alopecia.  All surviving animals displayed increases in body weight over their Day 0 values. The LD₅₀for this study was established at 7093 mg/kg for males, 5558 mg/kg for females, and 6318 mg/kg combined. 

Based on the results of this study, the oral LD50 for this material is greater than 5000mg/kg.  MRD-94-953 and classification as an acute oral toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given: comparable to guidelines/standards.

Qualifier:

no guideline followed

Principles of method if other than guideline:

2 male and 2 female rats dosed with 1, 2, 4, or 8 ml/kg of test substance via oral gavage.

GLP compliance:

no

Remarks:

prior to GLP

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Charles River CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 12 weeks
- Fasting period before study: overnight
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Route of administration:

oral: gavage

Doses:

1, 2, 4, 8 ml/kg

No. of animals per sex per dose:

2

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 9 days
- Frequency of observations and weighing: daily
- Other examinations performed: clinical signs

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 8 mL/kg bw

Remarks on result:

other: (~6984) mg/kg/bw)

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

4 mL/kg bw

Remarks on result:

other: (~3492 mg/kg/bw)

Mortality:

One female at the 4 ml/kg dosage died on day 7 of the study. The two females given dosages of 8 ml/kg died on day 7 of the study. No males at any dosage level died during the study.

Clinical signs:

other: One female from the 8 ml/kg dosage group became ataxic on day 4, a condition that persisted until the death of the animal on day 7.

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LD50 for female rats was 4 ml/kg bw. The LD50 for male rats was > 8 ml/kg (6984 mg/kg/bw). Given the relative density of 0.873 g/ml for the test substance, the LD50 for female rats is equivalent to 3492 mg/kg bw, at which level the test substance is considered not classifiable.

Executive summary:

This study was conducted to determine the acute oral toxicity of Hydrocarbons, C9, aromatics to rats. 2 male and 2 female rats dosed with 1, 2, 4, or 8 ml/kg of test substance via oral gavage. One female rat in the 4 ml/kg exposure group died, and both females in the 8 ml/kg exposure group died after showing signs of lethargy and ataxia. None of the male rats in the study died. The LD50 for female rats is then 4 ml/kg. The LD50 for male rats is > 8 ml/kg (6984 mg/kg bw). According to EU GHS guidelines, the test substance is not classified as being toxic.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3 492 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996/02/01-1996/02/15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Equivalent or similar to OECD Guideline 403. GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

5 animals used per species (not 10); dry air stream used to generate vapors so no particulate analysis was done

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Crl: CDBR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Inc.
- Sex: Male (5), Female (5) for each species
- Age at study initiation: 7 weeks
- Weight at study initiation: male 214-242g, female 170-214g
- Housing: Single housed
- Diet (e.g. ad libitum): PMI Feeds, Inc. Certified Rodent Diet #5002 ad libitum during nonexposure period; withheld during exposure
- Water (e.g. ad libitum): automatic watering system, ad libitum
- Acclimation period: 14 d and animals were examined once a day for viability


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68-76
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

The test material was heated to 137ºC to generate the vapor and resulting vapors were mixed with room air as both were drawn up through the generator and into the exposure chamber.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

a calibrated infrared vapor analyzer

Duration of exposure:

4 h

Concentrations:

Exposure Concentration (average actual): 6193 mg/m³
Exposure Concentration (nominal): 6528 mg/m³
Chamber size: 150 l
ATM pressure: slightly negative pressure to the room
Temperature: 25 deg C
Air flow rate: 30 (L/min)

No. of animals per sex per dose:

Male (5), Female (5) for each species

Control animals:

no

Details on study design:

The animals were individually housed in a 150l stainless steel whole body inhalation chamber that was under a slight negative pressure to the room and had an air flow of 30 (l/min). The exposure was 4 hrs plus equilibration time (~23 min) and air flow, temperature, and humidity were continuously monitored. Animals were observed for mortality and obvious toxic signs at 15 min intervals for the first hour of exposure and then once each hour until the termination of the exposure. Body weights for each animal were recorded prior to exposure and on days 7 and 14. A gross necropsy was performed on every animal.

Statistics:

Mean and standard deviation of body weight and body weight change by group and sex.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 6 193 mg/m³ air (analytical)

Remarks on result:

other: Concentration tested was the maximally attainable vapor concentration.

Mortality:

None

Clinical signs:

other: No adverse reactions were noted during exposure or the 14-day observation period that followed except for one female which had scabs on the head from day 4-9.

Body weight:

All animals gained body weight at the 7 and 14 day observation periods.

Gross pathology:

Necropsy examinations performed on all animals at the end of the observational period did not reveal any gross pathological alterations.

Summary of other acute inhalation toxicity studies.

End Point

Study Reference

REACH requirement

IUCLID Section

Study Name

Data Waiving

Waiving Justification

Species

Study Result Type

Test Guideline/Qualifier

Test Guideline/Guideline

Test Guideline/Deviations

Reliability

Rational For Reliability

GLP Compliance

Test Materials/Identity

Study Result

Reference Type

Reference Author

Reference Year

Reference Title

Bibliographic Source

Testing Laboratory

Reference Report No.

Owner Company

Company Study No.

Report Date

Data access

8.5.2 Acute toxicity inhalation

7.2.2

Inhalation

rat

Experimental result

No guideline followed.

2

Summary only of study.

No data

Shellsol A

LC50 > 10.2 mg/L

Study report

Coombs, AD, Blair, D, Doak, SM, Carter, BI

1977

The Acute Toxicity of Shellsol A

HSPA0690

Sittingbourne Research Centre

M(T)-1-77

Shell Chemicals Europe BV

June, 1977

yes

8.5.2 Acute toxicity inhalation

7.2.2

Acute Vapor Inhalation Toxicity Study - Albino Rats, Mice and Guinea Pig

rat, mice, guinea pig

Experimental result

Equivalent or similar to

OECD guideline 403

5 animals used per species (not 10); dry air stream used to generate vapors so no particulate analysis was done.

2

The study is scientifically sound, however, it was not performed in strict accordance with OECD guidelines.

No

MRD-ECH-74-22

LC50 > 14.4 mg/L

Study report

ANON

1975

Acute Vapor Inhalation Toxicity Study - Albino Rats, Mice and Guinea Pig

HSPA0153

Industrial BioTest Laboratories, Inc.

663-06262

ExxonMobil Petroleum & Chemical BVBA

75MRL17

27/03/1975

yes

8.5.2 Acute toxicity inhalation

7.2.2

The Acute 4 H Inhalation LC50 of Hydrogenated Shellsol A in Rats

rat

Experimental result

No guideline followed.

1

Well-documented study.

No

Hydrogenated Shellsol A

LC50 =14.0 mg/L

Study report

Blair, D

1982

The Acute 4 H Inhalation LC50 of Hydrogenated Shellsol A in Rats

HSPA0691

Sittingbourne Research Centre

Shell Chemicals Europe BV

SBGR.82.037

Jan. 1982

yes

Interpretation of results:

other: not classifiable

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LC50 was > 6193 mg/m³ (>6.193 mg/l) air. Based on the LC50 and other data, test substance MRD-95-374 is not classified under either the EU GHS guidelines or under the EU dangerous substances and preparations guidelines as the LC50 level exceeds the maximally attainable vapor
concentrations under the test conditions.

Executive summary:

Five male and five female rats were exposed to 6193 mg/m3 (>6.193 mg/l) air vapors of test material MRD-95-374 for 4 hrs. Animals were observed for 14 days. Animals continued to gain weight through day 14. There was no mortality and no gross pathological alterations noted in any of the animals. Based on an LC50 >6193 mg/m3 (>6.193 mg/L) air and other data, test substance Hydrocarbons,C9 aromatics is not classified under either the EU GHS guidelines or under the EU dangerous substances preparations guidelines as the LC50 level exceeds the maximally attainable vapor concentrations under the test conditions.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

From November, 15, 1994 to December 1, 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report in general agreement with OECD guideline 403-GLP

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

only one dose tested

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Inc.
- Age at study initiation: approximately 8-10 weeks
- Weight at study initiation: 225-296 grams
- Housing: individually
- Diet (e.g. ad libitum): ad libitum during non-exposure periods. Food withheld while animals were in chamber
- Water (e.g. ad libitum): ad libitum during non-exposure periods. Food withheld while animals were in chamber
- Acclimation period: eight days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): maintained range 20-24.4
- Humidity (%): maintained range of 40-70
- Photoperiod (hrs dark / hrs light): 12hrs dark / 12hrs light


IN-LIFE DATES: From: November 17, 1994 To: December 1, 1994

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 150 liter stainless steel inhalation chamber
- Exposure chamber volume: 150 liter
- Method of holding animals in test chamber:
- Source and rate of air: chamber operated under slight negative pressure to the room at an airflow of approximately 30.0 liters per minute
- Method of conditioning air:
- System of generating vapor: test material was delivered by a syringe pump to the inside of a heated glass counter current vapor generator
- Treatment of exhaust air:
- Temperature, humidity, pressure in air chamber: approximately 23.8 C


TEST ATMOSPHERE
- Brief description of analytical method used: vapor concentrations were determined during exposure by drawing chamber air through a calibrated infrared monitor. chamber concentrations were recorded at approximately 1 hour intervals and averaged to yield the mean chamber concentration for exposure
- Samples taken from breathing zone: yes



CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: highest attainable vapor concentration

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 4 h

Concentrations:

average actual vapor concentration of 4688 mg/m3 (± 72 mg/m3)

No. of animals per sex per dose:

10 animals (5 males; 5 females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed in chamber during exposure at 15, 30, and 45 minutes and at 1, 2, 3, and 4 hours. Animals were observed once daily for 14 days. Body weights were measured before exposure and on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other:

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4 688 mg/m³ air (analytical)

Remarks on result:

other: no mortality or gross systemic toxicity observed at this dose

Clinical signs:

other: all animals appeared normal during the 14-day post-exposure observation period, except one male with red ocular discharge on day 5 post-exposure

Body weight:

Body weight gain for all animals appeared normal throughout the observation period with the exception of one female whose weight remained unchanged from day 7 to day 14

Gross pathology:

all animals appeared normal at the gross postmortem examination

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LC50 for acute inhalation exposure to MRD-94-953 vapor is greater than the highest obtainable vapor concentration (4688 mg/m3). Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Executive summary:

The acute inhalation toxicity of MRD-94-953 was evaluated in ten Sprague-Dawley rats.  Animals were exposed for four hours to the maximum attainable vapor concentration of the test material (4688mg/m3) in individual inhalation chambers. Animals were observed for 14 days.  There were no mortality or gross pathological alterations noted in any of the animals.  Based on the conditions of this study, the LC50for vapors of MRD-94-953 are greater than 4688mg/m3. Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Reference 3

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Done in accordance to basic scientific principles.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Age at study initiation: 7-8 weels
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

Two rats of each sex age 7and 8 weeks were housed in a tubular glass chamber, and exposed for 4 hours to test atmospheres by the near saturation of air supplied to the test chamber. The animals were observed over the subsequent 14 days. Food and water were available to the animals at all times except for the 4 hour exposure period.

The concentration of solvent in the test atmosphere was monitored continuously during the exposure by means of a high temperature total hydrogen analyzer. The instrument was calibrated using a gravimetric procedure.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

high temperature total hydrogen analyzer

Duration of exposure:

4 h

Concentrations:

10.2 mg/L (approx 2000 ppm)

No. of animals per sex per dose:

two rats of each sex

Control animals:

no

Details on study design:

Two rats of each sex age 7and 8 weeks were housed in a tubular glass chamber, and exposed for 4 hours to test atmospheres by the near saturation of air supplied to the test chamber. The animals were observed over the subsequent 14 days. Food and water were available to the animals at all times except for the 4 hour exposure period.

The concentration of solvent in the test atmosphere was monitored continuously during the exposure by means of a high temperature total hydrogen analyzer. The instrument was calibrated using a gravimetric procedure.

Statistics:

none

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 10.2 mg/L air (nominal)

Remarks on result:

other: (approx 2000 ppm)

Mortality:

No mortality was noted.

Clinical signs:

other: Exposure produced lethargic behavior in male and female rats.

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LC50 was >10.2 mg/l (approx 2000 ppm). The LC50 for acute inhalation exposure to the test material vapor is greater than the highest obtainable vapor concentration. Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Executive summary:

The acute inhalation toxicity of the test material was evaluated in four CD rats.  Animals were exposed for four hours to the maximum attainable vapor concentration of the test material >10.2 mg/l (approx 2000 ppm) in individual inhalation chambers.  Animals were observed for 14 days.  There were no mortality or gross pathological alterations noted in any of the animals.  Based on the conditions of this study, the LC50 for vapors of Hydrocarbons, C9 Aromatics are greater than >10.2 mg/l (approx 2000 ppm). Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

6 193 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

From November 14, 1994 To November 29, 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report in agreement with OECD test guideline 402-GLP

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HRP Inc., Denver, PA
- Age at study initiation: Males: approximately 13 weeks; females: approximately 10 weeks
- Weight at study initiation: 2.05-2.43kg
- Housing: individually
- Diet (e.g. ad libitum): Based on recommendations of the animal supplier, in an effort to improve the health of the animals, the amount of feed administered to the animals was limited on a daily basis.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.3-21.1 °C
- Humidity (%): 40 to 60 percent relative humidity
- Photoperiod (hrs dark / hrs light): 12hrs dark /12 hrs light


IN-LIFE DATES: From: November 15, 1994 To: November 29, 1994

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal surface from the shoulder region to the lumbar region
- % coverage: at least 10% of the body surface
- Type of wrap if used: the gauze patch was secured to the trunk of the animal with a plastic sleeve


REMOVAL OF TEST SUBSTANCE
- Washing (if done): reverse osmosis water and paper towels
- Time after start of exposure: approximately 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000mg/kg

Duration of exposure:

24 hours

Doses:

2000mg/kg dose

No. of animals per sex per dose:

5 males; 5 females (nulliparous and non-pregnant)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made at 2 and 4 hours after dosing, and daily thereafter for a total of 14 days.
Body weights were recorded once prior to dosing initiation; on Days 0, 7, 14; and on the day of sacrifice. Dermal responses were evaluated on Day 1 (30 to 60 minutes after patch removal) and on Days 3, 7, and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: Clinical observations were made as to the nature, onset, severity, and duration of toxicological signs; Dermal responses were evaluated according to the Draize method of scoring.

Statistics:

Statistical analyses included means and standard deviations of body weights and body weight change by group and sex.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: no evidence of systemic toxicity under the conditions of this study at this dose

Clinical signs:

other: All animals survived to study termination. There were no treatment-related clinical signs. At the 2 and 4 hour observations, one female had mucoidal stool. At the Day 1 observation, one female was noted with a reddened nictitating membrane. These find

Gross pathology:

At the postmortem examination, four males and two females were noted with desquamation and/or eschar on the dose site which was consistent with their inlife dermal observations. The remaining male and three females had no macroscopic abnormalities.

Other findings:

Topical application of the test material elicited dermal irritation in all animals. At the Day 1 observation, eight animals had well-defined erythema and two animals had moderate/severe erythema. At the Day 3 observation, five animals had well-defined erythema, two animals had moderate/severe erythema, and one animal had severe erythema. At the Day 7 observation, four animals had very slight erythema, three animals had well-defined erythema, and one animal had severe erythema. On Day 14, three animals had very slight erythema, one animal had well-defined erythema, and four animals had severe erythema/slight eschar formation.

Edema was observed in all animals. At the Day 1 observation, one animal had very slight edema, one animal had slight edema, and eight animals had moderate edema. At the Day 3 observations, one animal had very slight edema and four animals had slight edema. Edema was not observed in any animal on Day 7. At the Day 14 observation, one animal had slight edema.

Other dermal observations included atonia, cracking, desquamation, eschar, exfoliation, fissuring, and leathery texture of the dose site.

Severe dermal irritation from mechanical damage at undamming was observed in all ten animals at sleeve removal and in nine animals at the Day 1 observation. This irritation was not scored.

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the dermal LD50 for MRD-94-953 is greater than 2000 mg/kg. Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Executive summary:

The acute toxicity of MRD-94-953 was evaluated following its application to the clipped backs of ten New Zealand White rabbits.  A single dose of 2000 mg/kg of the test material was applied to not less than 10% of the body surface, covered with a gauze patch, and secured with non-irritating tape and a plastic sleeve.  Clinical observations were performed 2 and 4 hours after dosing, and once per day thereafter for a total of 14 days.  Dermal responses were evaluated on Days 1, 3, 7, and 14 according to the Draize method of scoring.  Body weights were recorded the day prior to dosing, the day of dosing (Day 0), and on Days 7 and 14.  Application of MRD-94-953 at a dose level of 2000 mg/kg showed no evidence of systemic toxicity under the conditions of this study and all animals survived to study termination.  There were no treatment-related clinical signs.  Dermal irritation was the most significant finding and was observed in the majority of animals throughout the study. 

 

Based on the results of this study, the dermal LD₅₀ for MRD-94-953  is greater than 2000 mg/kg in the rabbit. Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984/03/01-1984/03/15

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Similar to OECD Guideline 402: Acute Dermal Toxicity

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Used 3 male and 3 female rabbits instead of recommended 5 for each sex; occlusive patch used

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazelton Dutchland, Inc.
- Sex: male (3), female (3)
- Age at study initiation: appox. 19 weeks
- Weight at study initiation: 2,99-3.61 kg
- Housing: Individually
- Diet (e.g. ad libitum): Purina certified rabbit chow HF, ad libitum
- Water (e.g. ad libitum): Automatic watering system, ad libitum
- Acclimation period: 52 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-71
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal surface
- Type of wrap if used: gauze patch covered with a plastic sleeve


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Distilled water and paper towels
- Time after start of exposure: 24 hrs


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3160 mg/kg
- Concentration (if solution): Assumed to be 100%; density of 0.8578 g/ml
- Constant volume or concentration used: yes

Duration of exposure:

24 hrs

Doses:

one dose: 3160 mg/kg
volume: 11-13 ml

No. of animals per sex per dose:

3 males, 3 females

Control animals:

no

Details on study design:

SCORING SYSTEM: Draize scale
- Duration of observation period following administration: 2, 4, 24 hrs after dosing and once per day thereafter for 14 days
- Dermal response observations: 24 hrs, 3, 7, 10, and 14 days
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight

Statistics:

The mean and standard deviations for the body weights and body weight changes were calculated.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 160 mg/kg bw

Mortality:

There were no animal deaths prior to study termination.

Clinical signs:

other: Overall low incidence of clinical in-life observations. -Most frequently noticed: desquamation, atonia, leathery skin, and eschar. At the termination of the study all animals exhibited desquamation. -Low Incidences: soft stool and small amount of stool,

Gross pathology:

All animals displayed very slight to well-defined erythema from day 0 to day 7. By day 14, only two animals still showed erythema; one having a very slight grade noted. Many animals exhibited very slight edema in a similar time frame.

Desquamation (6 animals), atonia (2 animals), leathery skin (2 animals), and eschar (1 animal) were noted through out the observational time period. At the termination of the study all animals exhibited desquamation.

Two animals were noted as being hyperactive and having a red nasal discharge after dosing. There was a single incidence of slight vocalization following dosing.

Other findings:

GROSS POSTMORTEM EXAMINATION
Alopecia for 1 animal (abdominal).
Severe erythema for 1 animal at the dosing site.
Desquamation for all animals at the dosing site.

Summary of other acute dermal toxicity studies.

End Point

Study Reference

REACH requirement

IUCLID Section

Study Name

Data Waiving

Waiving Justification

Species

Study Result Type

Test Guideline/Qualifier

Test Guideline/Guideline

Test Guideline/Deviations

Reliability

Rational For Reliability

GLP Compliance

Test Materials/Identity

Study Result

Reference Type

Reference Author

Reference Year

Reference Title

Bibliographic Source

Testing Laboratory

Reference Report No.

Owner Company

Company Study No.

Report Date

Data access

8.5.3 Acute toxicity, dermal route

7.2.3

Acute percutaneous toxicity

rat

Experimental result

According to

Noakes, D.N., and Sanderson, D.M. (1969). A method for determining the dermal toxicity of pesticides. Br. J. Industr. Med.,26, 59-64.

2

Summary only of study.

No data

Shellsol A

LD50 > 4 ml/kg

Study report

Coombs, AD, Blair, D, Doak, SM, Carter, BI

1977

The Acute Toxicity of Shellsol A

HSPA0692

Sittingbourne Research Centre

M(T)-1-77

Shell Chemicals Europe BV

June, 1977

yes

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LD50 > 3160 mg/kg based on these data, MRD-83-208 is not classified under EU requirements for dangerous substances and preparations. MRD-83-208 is also not classified under GHS guidelines.

Executive summary:

Three male and female rabbits were exposed to MRD-83 -208 for 24 hrs via an occluded patch. Dermal evaluations occurred at 24 hrs post patch removal and on days 3, 7, 10, 14. Exposure had no affect on viability; all animals survived the exposure. It is concluded that the LD50 in this situation is greater than 3160 mg/kg. MRD-83 -208 is not classified under EU dangerous substances and preparations guidelines. MRD-83 -208 is also not classified under GHS guidelines.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

The acute toxicity of Hydrocarbons, C9 aromatics has been fully evaluated.  All of the animal studies were performed in a manner similar or equivalent to currently established OECD guidelines.  Based on these data, hydrocarbons, C9, aromatics have a low order of acute toxicity by the oral, dermal, and inhalation routes of exposure.

Hydrocarbons, C9 Aromatics:

Acute toxicity studies on Hydrocarbons, C9, aromatics are available for each of the three potential routes of exposure. Additional oral toxicity and inhalation toxicity studies are also available. The studies discussed below represent the key studies.

 

Male rats exposed orally to hydrocarbons, C9, aromatics exhibited no mortality at the highest concentration tested and therefore the LD₅₀ was >8 mL/Kg. One female rat at the 4 mL/Kg dose and two females at the 8 mL/Kg dose died on day 7 of the study. The LD₅₀ for female rats was 4 mL/Kg (equivalent to 3492 mg/Kg bw).

 

The acute study conducted via the inhalation route resulted in no acute toxicity at the maximally attainable vapor concentration, which was 6193 mg/m³.

 

No mortality was observed at the highest dermal dose examined, resulting in an LD₅₀ >3160 mg/Kg.

Hydrocarbons, C10 Aromatics, >1% Naphthalene:

The acute toxicity of hydrocarbons, C10 aromatics, >1% napthalene has been fully evaluated. All of the animal studies were performed in a manner similar or equivalent to currently established OECD guidelines. Hydrocarbons, C10 aromatics, is minimally toxic via ingestion where the LD50 is 6318 mg/Kg, via dermal exposure where the LD50 is >2000mg/Kg, and by inhalation where the LC50 >4688 mg/m3. 

 

Based on available data, Hydrocarbons, C9, aromatics have a low order of acute toxicity by the oral, dermal, and inhalation routes of exposure and are not classifiable under EU CLP.

Justification for classification or non-classification

Based on available data, Hydrocarbons, C9, aromatics can be considered to be minimally toxic via ingestion, via dermal exposure, and by inhalation and do not warrant classification under the new Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP). On the basis of available physical and chemical property data (hydrocarbon fluid, viscosity ≤ 20.5 mm²/s), Hydrocarbons, C9, aromatics are classified under EU CLP guidelines as a Category 1 aspiration hazard (H304).