1-dodecylpyridinium chloride

Endpoint summary

Description of key information

Repeated dose toxcity: Oral

The No Observed Adverse Effect Level (NOAEL) for the test chemical was considered to be 40 mg/kg bw/day in CD-1 mice after repeated exposure via oral route.

 

Repeated inhalation study:

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance 1-dodecylpyridinium chloride (104-74-5) which is reported as 0.000034502838 mmHg at 25 C. Thus, exposure to inhalable dust, mist and vapour of the chemical 1-dodecylpyridinium chloride is highly unlikely. Therefore this study is considered for waiver.

Repeated dermal study;

The acute toxicity value for 1-dodecylpyridinium chloride (104-74-5) (as provided in section 7.2.3) is >2000 mg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that 1-dodecylpyridinium chloride shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that 1-dodecylpyridinium chloride shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

experimental data of read across substances

Justification for type of information:

data from handbook or collection of data

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Weight of evidence prepared from various publication mention below
1,Repeated dose oral toxicity study was performed to determine the toxic nature of the test chemical.
2,Subchronic repeated dose oral toxicity study for the test chemical was conducted in CD-1 mice.

GLP compliance:

not specified

Limit test:

no

Species:

other: 1. mouse/2. & 3 rat

Strain:

other: 1. CD-1 / 2. Sprague Dawley rats /3.Wistar

Details on species / strain selection:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

other: 1&2.oral: feed/3.oral gavage

Details on route of administration:

No data

Vehicle:

other: diet

Details on oral exposure:

1. PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with feed at dose level of 0, 20, 60, 120, 200 or 600 mg/Kg/day

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): Feed
- Concentration in vehicle: 0, 20, 60, 120, 200 or 600 mg/Kg/day
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data

2.
PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with feed at dose level of 0, 40, 200 and 1000 mg/kg/day

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): Feed
- Concentration in vehicle: 0, 40, 200 and 1000 mg/kg/day
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

1. 89 day (males) or 90 days
2. 28 days
3.Males were treated for 43 days while females were treated from the beginning of the study until day 4 of lactation.

Frequency of treatment:

1&3. daily
2. Continuous

Remarks:

0, 20, 60, 120, 200 or 600 mg/Kg/day / 1

Remarks:

0, 40, 200 and 1000 mg/kg/day / 2

Remarks:

0, 50, 150, or 400 mg/kg bw/day/3

No. of animals per sex per dose:

1. 15/sex/group
2. Total: 24 males and 24 females
0 mg/Kg/day: 6 males and 6 females
40 mg/Kg/day: 6 males and 6 females
200 mg/Kg/day: 6 males and 6 females
1000 mg/Kg/day: 6 males and 6 females

Control animals:

yes, concurrent vehicle

Details on study design:

not specified

Positive control:

not specified

Observations and examinations performed and frequency:

1. Clinical symptoms, body weight and mortality
2. &3
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily for health and weekly for palpation
- Cage side observations checked in table [No.?] were included. Rats were observed twice daily throughout the treatment period for evidence of reaction to treatment or ill health. A detailed weekly examination was conducted, including palpation.

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule: No data

BODY WEIGHT: Yes
- Time schedule for examinations: Body weights were recorded on the day that treatment commenced, at twice weekly intervals during the treatment period and immediately before necropsy.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, weekly
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes / No / No data
- Time schedule for examinations:

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data

HAEMATOLOGY: Yes
- Time schedule for collection of blood: On Day 28 of treatment, prior to sacrifice
- Anaesthetic used for blood collection: No data
- Animals fasted: Yes, overnight fasting
- How many animals: All animals
- Parameters checked in table [No.?] were examined. Packed cell volume, hemoglobin concentration, erythrocyte count, mean cell hemoglobin concentration, mean cell volume, mean cell hemoglobin and total and differential leukocyte count.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: On Day 28 of treatment, prior to sacrifice
- Animals fasted: Yes, overnight
- How many animals: All animals
- Parameters checked in table [No.?] were examined. alkaline phosphatase activity, alanine amino-transferase activity, aspartate amino-transferase activity, urea concentration, glucose concentration, total bilirubin concentration, creatinine concentration, total protein concentration, electrophoretic protein fractions and sodium, potassium, chloride, calcium and inorganic phosphorus concentrations

URINALYSIS: No data
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. No data

NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
- Battery of functions tested: No data sensory activity / grip strength / motor activity / other: No data

OTHER: No data

Sacrifice and pathology:

1. GROSS PATHOLOGY: Not specified
HISTOPATHOLOGY: Yes

2. GROSS PATHOLOGY: Yes, at the end of the 28-day treatment period, all rats were sacrificed and subjected to a detailed necropsy. The following organs were weighed: adrenals, kidneys, heart, spleen, testes and liver.

HISTOPATHOLOGY: Yes, adrenals, kidneys, heart, spleen, lymph node (mesenteric) and liver were examined microscopically.
3. GROSS PATHOLOGY: Not specified
HISTOPATHOLOGY: Yes

Other examinations:

Not specified

Statistics:

1. Not specified
2. Student's t-test, Dunnett's test or Fisher's exact probability test

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

1. At 3000 ppm animals exhibited general ill health with hunched posture, emaciation.
2. No signs of reaction to treatment were observed during the treatment period.
3.Intermittent occurrence of reddish nasal secretion was reported in two males in the 400mg/kg bw dose group. Bedding found in the mouth and salivation during days 5 to 7 of gestation were reported in one female in the 400mg/kg bw dose group. These effects may have been due to oral discomfort associated with treatment with the chemical.

Mortality:

mortality observed, treatment-related

Description (incidence):

1. All animals at 3000 ppm died except for one male. Death was attributed to treatment related malnutrition and dehydration
2. No mortality was noted in the treated animals

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

1. At 1000 ppm, males showed decreased body weight gain. Body weight effects were minimal at 1000 ppm
2. Body weight gain was unaffected by treatment.
3.There were statistically significant reductions in body weight gain in males in the 400mg/kg bw dose group compared with controls during part of the pre-pairing period (days 4–8). The reduction was less marked during the end of the pre-pairing period. Reduced body weight gain similar to males was reported in females in the 400mg/kg bw dose group when compared with controls but did not reach statistical significance.

Food consumption and compound intake (if feeding study):

effects observed, non-treatment-related

Description (incidence and severity):

3.There were statistically significant reductions in food consumption in males in the 400mg/kg bw dose group compared with controls during part of the pre-pairing period (days 4–8). The reduction was less marked during the end of the pre-pairing period. The study authors reported the transient reduction in food consumption to be not adverse.

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Description (incidence and severity):

2. Results of the hematology did not reveal any treatment-related effects.

Clinical biochemistry findings:

no effects observed

Description (incidence and severity):

2. Blood chemistry examination revealed a slight increase in alanine amino-transferase activity in animals receiving 1000 mg/kg/day when compared with controls.
3.In both sexes in the 400mg/kg bw dose group, there were higher concentrations of aspartate aminotransferase (not statistically significantly different), of alanine aminotransferase (males only) and of alkaline phosphatase. In one male, a pale discoloured liver was reported during necropsy. Other statistically significant differences (creatinine, potassium, chloride, protein and
albumin) were within the range of the historical controls

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

2. Organ weight analysis and macroscopic pathology did not reveal any treatment-related effects.
3.There were no significant effects on organ weights reported except for the testes and epididymides of males.

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

1. at 3000 ppm animals exhibited distension and/or watery contents of the intestines.
2. Histologic evaluations revealed statistically significant increases in histiocytic hyperplasia in the mesenteric lymph nodes in male and female rats receiving 1000 mg/kg/day. A few animals from the 200 mg/kg day dosage group also were affected: however, the group incidence was not statistically significantly different from the control.

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Dose descriptor:

NOAEL

Effect level:

200 other: mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

histopathology: non-neoplastic

mortality

Dose descriptor:

NOAEL

Effect level:

40 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No significant effects were noted at the mentioined dose level

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Conclusions:

The No Observed Adverse Effect Level (NOAEL) for the test chemical was considered to be 40 mg/kg bw/day in CD-1 mice after repeated exposure via oral route.

Executive summary:

Data available from various publication to determine the toxic nature of test substance. The studies are as mentioned below:

In a subchronic or Prechronic exposure study the test chemical was fed to CD-1 mice (15/sex/group) in the diet at 0 (vehicle = diet), 100, 300, 600, 1000 or 3000 ppm daily for 89 day (males) or 90 days (approx. equivalent to0, 20, 60, 120, 200 and 600 mg/kg bw/day). At 1000 ppm (200 mg/Kg/day), males showed decreased body weight gain. All animals at 3000 ppm (600 mg/Kg/day) died except for one male, also animals exhibited general ill health with hunched posture, emaciation, distension and/or watery contents of the intestines. Death was attributed to treatment related malnutrition and dehydration. Body weight effects were minimal at 1000 ppm, whereas death occurred at 3000 ppm in both sexes. Thus, the No Observed Adverse Effect Level (NOAEL) for the test chemical was considered to be 200 mg/kg bw/day in CD-1 mice after repeated exposure via oral route.

Repeated dose oral toxicity study was performed to determine the toxic nature of the test chemical. The study was performed using male and female Sprague Dawley rats at dose level of0, 40, 200 and 1000 mg/kg/day. The doses for the main study were based on the dose range finding study. The animals were dosed continuously for 28 days and observed for clinical signs, mortality, body weight and food consumption changes, hematology and clinical chemistry parameters and were subjected to gross pathology and histopathology.No signs of reaction to treatment and no mortality were observed during the treatment period. Food consumption, body weight and food utilization (amount of food consumed per unit of body weight gain) were unaffected by treatment. Results of the hematology did not reveal any treatment-related effects. Blood chemistry examination revealed a slight increase in alanine amino-transferase activity in animals receiving 1000 mg/kg/day when compared with controls. Organ weight analysis and macroscopic pathology did not reveal any treatment-related effects. Histologic evaluations revealed statistically significant increases in histocytic hyperplasia in the mesenteric lymph nodes in male and female rats receiving 1000 mg/kg/day. A few animals from the 200 mg/kg day dosage group also were affected: however, the group incidence was not statistically significantly different from the control. Based on the observations made, No observed adverse effect level (NOAEL) for the test chemical is considered to be 40 mg/Kg/day.

Study 3

A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test was performed in male and female Wistar rats. The test material in dose concentration0, 50, 150, or 400 mg/kg bw/day was administered by oral gavage route.Males were treated for 43 days while females were treated from the beginning of the study until day 4 of lactation. All the animals were observed for clinical signs and mortality. Body weight and food consumption also noted.Organ weights, Haematology, Clinical chemistry, Histopathology were performed.

Intermittent occurrence of reddish nasal secretion was reported in two males in the 400mg/kg bw dose group. Bedding found in the mouth and salivation during days 5 to 7 of gestation were reported in one female in the 400mg/kg bw dose group. These effects may have been due to oral discomfort associated with treatment with the chemical. There were statistically significant reductions in food consumption and body weight gain in males in the 400mg/kg bw dose group compared with controls during part of the pre-pairing period (days 4–8). The reduction was less marked during the end of the

pre-pairing period. Reduced body weight gain similar to males was reported in females in the 400mg/kg bw dose group when compared with controls but did not reach statistical significance. The study authors reported the transient reduction in food consumption to be not adverse. In males in the 400mg/kg bw dose group, there was a statistically significant increase (1.8-fold increase) in the number of neutrophils compared with controls, and a decrease in the percentage of lymphocytes. Additionally, the haemoglobin and haematocrit values were statistically significantly lower than controls, but close to historical control data. Statistically significant decreases in mean corpuscular haemoglobin and basophil levels were within the range of historical controls. In females, all values from haematology examinations were with historical control values.In both sexes in the400mg/kg bwdose group, there were higher concentrations of aspartate aminotransferase (not statistically significantly different), of alanine aminotransferase (males only) and of alkaline phosphatase. In one male, a pale discoloured liver was reported during necropsy. Other statistically significant differences (creatinine, potassium, chloride, protein and albumin) were within the range of the historical controls. There were no significant effects on organ weights reported except for the testes and epididymides of males.In the majority of male and female rats at all doses tested, in the heart, a minimal to moderate multifocal dose-dependent cardiomyopathy (myocardial necrosis and/or degeneration with mononuclear inflammatory infiltration, and often accompanied by

fibrosis/fibroplasia) .At all doses tested, minimal to moderate foamy macrophage accumulation was observed in the lungs. A higher incidence and severity of these effects was reported in males compared with females. Hence LOAEL (lowest observed adverse effect level) of 50 mg/kg bw/day was considered for systemic toxicity. When male and female wistar rats were treated with test material orally.

 

Based on the data available for the target chemical and its read across chemical, Methyl(trioctyl)azanium chloride (CAS no 5137 -55 -3) is not likely to be toxic as per the criteria mentioned in CLP regulation.If however the content of CAS # 68814-95 -9 (STOT RE Cat. 1 for effects on the heart) is at or greater than 1 % (but less than 10 %), a classification withSTOT RE Cat. 2for potential effects on the heart is warranted.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

40 mg/kg bw/day

Study duration:

subchronic

Species:

mouse

Quality of whole database:

Data is Klimisch 2 and from authoritative database

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Waiver

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Waiver

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity: Oral

Data available for the test chemicals was reviewed to determine its toxic nature. The studies are as mentioned below:

In a subchronic or Prechronic exposure study the test chemical was fed to CD-1 mice (15/sex/group) in the diet at 0 (vehicle = diet), 100, 300, 600, 1000 or 3000 ppm daily for 89 day (males) or 90 days (approx. equivalent to0, 20, 60, 120, 200 and 600 mg/kg bw/day). At 1000 ppm (200 mg/Kg/day), males showed decreased body weight gain. All animals at 3000 ppm (600 mg/Kg/day) died except for one male, also animals exhibited general ill health with hunched posture, emaciation, distension and/or watery contents of the intestines. Death was attributed to treatment related malnutrition and dehydration. Body weight effects were minimal at 1000 ppm, whereas death occurred at 3000 ppm in both sexes. Thus, the No Observed Adverse Effect Level (NOAEL) for the test chemical was considered to be 200 mg/kg bw/day in CD-1 mice after repeated exposure via oral route.

Repeated dose oral toxicity study was performed to determine the toxic nature of the test chemical. The study was performed using male and female Sprague Dawley rats at dose level of0, 40, 200 and 1000 mg/kg/day. The doses for the main study were based on the dose range finding study. The animals were dosed continuously for 28 days and observed for clinical signs, mortality, body weight and food consumption changes, hematology and clinical chemistry parameters and were subjected to gross pathology and histopathology.No signs of reaction to treatment and no mortality were observed during the treatment period. Food consumption, body weight and food utilization (amount of food consumed per unit of body weight gain) were unaffected by treatment. Results of the hematology did not reveal any treatment-related effects. Blood chemistry examination revealed a slight increase in alanine amino-transferase activity in animals receiving 1000 mg/kg/day when compared with controls. Organ weight analysis and macroscopic pathology did not reveal any treatment-related effects. Histologic evaluations revealed statistically significant increases in histocytic hyperplasia in the mesenteric lymph nodes in male and female rats receiving 1000 mg/kg/day. A few animals from the 200 mg/kg day dosage group also were affected: however, the group incidence was not statistically significantly different from the control. Based on the observations made, No observed adverse effect level (NOAEL) for the test chemical is considered to be 40 mg/Kg/day.

Based on the data available for the test chemicals, the No Observed Adverse Effect Level (NOAEL) for the test chemical was considered to be 40 mg/kg bw/day in CD-1 mice after repeated exposure via oral route.

Repeated inhalation study:

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance 1-dodecylpyridinium chloride (104-74-5) which is reported as 0.000034502838 mmHg at 25 C. Thus, exposure to inhalable dust, mist and vapour of the chemical 1-dodecylpyridinium chloride is highly unlikely. Therefore this study is considered for waiver.

Repeated dermal study;

The acute toxicity value for 1-dodecylpyridinium chloride (104-74-5) (as provided in section 7.2.3) is >2000 mg/kg body weight. Also, given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that 1-dodecylpyridinium chloride shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that 1-dodecylpyridinium chloride shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

Based on the data available for the target chemical and applying weight of evidence is not likely to be toxic as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data available for the test chemical not likely to exhibit toxic nature upon repeated exposure by oral, inhalation and dermal route of exposure and hence is not likely to classify as per the criteria mentioned in CLP regulation.