Hydrocarbons, C9-C10, aromatics, >1% naphthalene

Acute Toxicity: oral

Administrative data

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:

Hydrocarbons, C9-C10, aromatics, >1% Naphthalene are a combination of Hydrocarbons, C9 Aromatics and Hydrocarbons, C10-C12 Aromatics. Read across data is available for Hydrocarbons, C9 Aromatics and Hydrocarbons, C10-C12 Aromatics and the worst case scenario for each end point has been presented.

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

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:

Hydrocarbons, C9-C10, aromatics, >1% Naphthalene are a combination of Hydrocarbons, C9 Aromatics and Hydrocarbons, C10-C12 Aromatics. Read across data is available for Hydrocarbons, C9 Aromatics and Hydrocarbons, C10-C12 Aromatics and the worst case scenario for each end point has been presented.

Reason / purpose for cross-reference:

read-across source

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:

This data is being read across from the source study that tested Hydrocarbons, C10, aromatics, >1% naphthalene based on analogue read across.

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 LD₅₀ for 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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

Hydrocarbons, C10, aromatics, >1% naphthalene

EC Number:

919-284-0

Molecular formula:

None available - not a single isomer - see remarks

IUPAC Name:

Hydrocarbons, C10, aromatics, >1% naphthalene

Details on test material:

- Name of test material (as cited in study report): MRD-94-953
- Physical state: Colorless liquid
- Analytical purity: assumed to be 100%
- Stability under test conditions: Not documented. Material stable under normal conditions
- Storage condition of test material: Room temperature

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 7 093 mg/kg bw

95% CL:

> 6 142 - < 8 190

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 5 558 mg/kg bw

95% CL:

> 4 592 - < 6 726

Effect levels 3

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.

Applicant's summary and conclusion

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 LD₅₀ for 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.