Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
67 mg/kg bw/day
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Acute/short-term local effects/ Long-term exposure local effects


DCBS showed only very slight and transient skin and eye irritation in guideline studies performed according to GLP with rabbits (Monsanto Co. 1985). No classification is required.


 


DCBS was negative in a guinea pig maximization assay (Monsanto Co. 1985). In a read across approach, where physicochemical data and toxicological findings of DCBS, CBS, TBBS and MBS were compared; consistencies in acute toxicity (oral and dermal), skin and eye-irritation, as well as in repeated dose toxicity were found. The substances CBS, TBBS and MBS were all classified as skin sensitizer in humans. Based on this finding and on the similarities noted in toxicity parameter a moderate skin sensitizing potential of DCBS in humans is suggested (Skin Sens. 1B).


 


Acute/short-term exposure systemic effects:


The acute toxicity of the test substance DCBS is very low after oral and dermal administration; LD50 values of >5000 mg/kg bw were obtained. Due to the very low oral and dermal acute toxicity of DCBS it is proposed to limit exposure peaks to a factor of 8. This approach is generally in line with the regulatory procedure in Germany (see Technical Rule for Hazardous Substances 900).


 


(DNEL short-term systemic dermal: 66.7 mg/kg bw/day x 8 = 534 mg/kg bw/day)


Revision of the risk assessment revealed though that there is no need for this acute DNEL.


In three limited inhalation studies with the test substances CBS, TBBS and MBS (Monsanto Co. 1981) exposed rats exhibited occasional nasal irritation which appeared to be concentration related (no more data). These findings were observed immediately after the 6 hour exposure period and disappeared by the next morning. Since the animals recovered from this lesion within 24 hours and these findings could not be correlated to histopathologic effects observed, the observation of nasal irritation in few test substance-exposed animals was not considered to be toxicologically adverse. To cover possible irritating effects no peak exposure factor was added in consistency with DNEL calculations for CBS, TBBS and MBS. For DCBS no additional exposure peak factor is added for the inhalation route.


(DNEL short-term systemic inhalation: 5.2 mg/m3 x 1 = 5.2 mg/m3r)


Revision of the risk assessment revealed though that there is no need for this acute DNEL.


DNEL long-term exposure systemic: Oral:


Several repeated dose studies and reproduction/developmental toxicity studies were performed to evaluate the repeated dose toxicity of DCBS. The consistent finding made in all studies is a reduction of body weight, body weight gain and/or food consumption in treated animals. Overall, a NOAEL of 36.9 mg/kg bw and day is taken for the risk assessment, which based on the findings from the 90-day feeding study (Monsanto Co. 1989).


 


DNEL calculation


Worker DNEL long-term systemic for oral route


Startpoint: 36.9 mg/kg bw and day 90-day feeding study (Monsanto Co. 1989).


Differences in absorption Abs (oral-rat) / Abs (oral-human): 1


     => Corrected NOAEL 36.9 mg/kg bw/day  


Interspecies differences: Allometric scaling: 4


Remaining interspecies differences: 2.5


 Intraspecies differences: 5


 Differences in duration of exposure (sub- chronic to chronic): 1*


Dose response and endpoint specific/severity issues: 1


Quality of database: 1


 Overall factor (product of individual factors):  50   


 =>Worker DNEL long-term for oral route-systemic: 0.74 mg/kg bw/day


* In several repeated dose studies the NOAEL and or LOAEL are in the same range; consistent findings in subacute, subchronic and reproduction/ developmental toxicity studies indicated by a reduction of body weight, body weight gain and/or food consumption.


 


 


Worker DNEL long-term systemic for dermal route


Startpoint: NOAEL (read across apprach): 2000 mg/kg bw and day subacute dermal studies in rabbits (Monsanto studies CBS, TBBS, MBS 1981)


Differences in absorption Abs (dermal-rabbit) / Abs (dermal-human): 1


=> Corrected NOAEL 2000 mg/kg bw/day


Interspecies differences: Allometric scaling: 2.4


Remaining interspecies differences: 2.5


Intraspecies differences: 5


Differences in duration of exposure (subacute to chronic): 1*


Dose response and endpoint specific/severity issues: 1


Quality of database: 1


Overall factor (product of individual factors): 30


=>Worker DNEL long-term for dermal route-systemic: 66.7 mg/kg bw/day


*No specific systemic effects noted for the dermal route, thus a factor of 1 as recommended for the oral route is suggested (the NOAEL and or LOAEL of DCBS are in the same range; consistent findings in subacute, subchronic and reproduction/ developmental toxicity studies indicated by a reduction of body weight, body weight gain and/or food consumption).


 


 


Worker DNEL long-term systemic for inhalation route


Startpoint: 36.9 mg/kg bw and day 90-day feeding study (Monsanto Co. 1989).


Respiratory volume rat (sRV) (worker (8 h): 1/0.38): 2.632


Differences in respiratory volume (default factor "light activity worker": 0.67


Differences in absorption Abs (oral-rat) / Abs (inhalation-human): 1


 => Corrected NOAEC 65.1 mg/m3 


Interspecies differences: Allometric scaling: 1


Remaining interspecies differences: 2.5


 Intraspecies differences: 5


 Differences in duration of exposure (sub- chronic to chronic): 1*


Dose response and endpoint specific/severity issues: 1


Quality of database: 1


 Overall factor (product of individual factors):  12.5


 =>Worker DNEL long-term for inhalation route-systemic: 5.2 mg/m3


* In several repeated dose studies the NOAEL and or LOAEL of DCBS are in the same range; consistent findings in subacute, subchronic and reproduction/ developmental toxicity studies indicated by a reduction of body weight, body weight gain and/or food consumption.


 


 


DNEL fertility:


The reproductive toxicity of the test substance DCBS was evaluated in three reproduction/developmental toxicity studies (Ema 2007, 2007b, 2008). In two studies adverse effects on reproduction were noted in treated animals in the range of maternal toxicity. In the reproduction/developmental study (Ema 2007b) adverse effects on reproduction was indicated by a significant lower number of implantations, pups delivered and decreased pup weights at 6000 ppm and 10000 ppm (ca. 476 and 707 mg/kg bw and day in females). These effects are in the range of maternal toxicity, indicated by reduced body weight gain and food consumption at 3000 ppm and higher (ca. 264 mg/kg bw and day). Adverse effects on reproduction was noted in the gavage study (Ema 2007) at 400 mg/kg bw and day in the range of severe maternal toxicity. However, in the two-generation study no significant changes in reproductive indices were noted in any generation even at the highest dose 4500 ppm (ca. 291 mg/kg bw and day). Maternal toxicity was indicated by a reduced body weight, body weight gain and food consumption in F0 females at 4500 ppm. The two-generation study is considered to be the most relevant study. Thus, based on the finding discussed above, the NOAEL fertility (foetal) is 4500 ppm (ca. 291 mg/kg bw and day) and the NOAEL fertility (maternal) is 600 ppm (ca. 54 mg/kg bw and day). Based on the findings of the two-generation study it was concluded that the DNEL long-term exposure systemic covered the DNEL fertility toxicity.


 


DNEL developmental toxicity:


The developmental toxicity of DCBS was evaluated in a repeated dose study with reproduction/developmental toxicity screening test (OECD TG 422; Ema 2007). Severe maternal toxic effects like mortality and clinical signs like decreased body weights, changes in blood chemistry and/or histopathology were noted in dams at 400 mg/kg bw and day. At this dose, all dams lost their litters at delivery or by day 4 of lactation. Thus, the authors concluded, that the NOAEL developmental (maternal/foetal) is 100 mg/kg bw and day. In a two-generation study (OECD TG 416; Ema 2008) no substance-related mortality and clinical signs were noted across generations up to the highest concentration evaluated (ca. 416 mg/kg bw and day in F0 females), whereas reduction of body weight gain in parental animals and offspring was consistently observed throughout the generations in that dose group. The isolated observation of slight delays in preputial separation reported in male offspring and the slight delays in vaginal opening and transient reduced uterus weights in weanling females are of questionable relevance and mainly observed at the toxic dose. Based on the reported decrease in body weight and body weight gain in F1 and F2 offspring, body weight, body weight gain and food consumption in F0 animals at 4500 ppm, the maternal and developmental NOAEL values are 600 ppm (ca. 54 mg/kg bw and day). Based on the findings of the two-generation study it was concluded that the DNEL long-term exposure systemic covered the DNEL for maternal and developmental toxicity.


 


 


In a GLP OECD 414 study eighty-eight mated female New Zealand White rabbits were assigned to four groups of 22 animals each. The test item, N,N-dicyclohexylbenzothiazole-2-sulphenamide, was administered once daily by oral gavage from Days 6 to 28 post-coitum at doses of 100, 300 and 1000 mg/kg/day (Groups 2, 3 and 4, respectively). Rabbits of the control group received the vehicle, 1% aqueous carboxymethyl cellulose with 0.1% Tween-80, alone. Females were checked daily for the presence of clinical signs. Food consumption and body weight were determined at periodic intervals. Formulations prepared on one day during treatment were analyzed for accuracy and homogeneity. On Day 29 post-coitum, all animals were subjected to an examination post-mortem and external, thoracic and abdominal macroscopic findings were recorded. A laparohysterectomy was performed on each female. The uteri, placentae and ovaries were examined, and the numbers of fetuses, early and late resorptions, total implantations and corpora lutea were recorded. Gravid uterine weights were recorded, and net body weights and net body weight changes were calculated. The fetuses were weighed, sexed and examined for external, visceral and skeletal malformations and developmental variations. All live fetuses were euthanized. Approximately, one half of the fetuses were decapitated and the heads were fixed in Bouin’s fixative. All fetuses were dissected and examined for visceral anomalies and subsequently fixed in 96% aqueous ethanol. Following staining with Alizarin Red S, skeletons of all fetuses of all groups were examined.


 


No maternal toxicity and no developmental toxicity was observed in the 100, 300 and 1000 mg/kg/day groups.Based on the results in this prenatal developmental toxicity study in rabbits the maternal and developmental No Observed Adverse Effect Level (NOAEL) for N,N-dicyclohexylbenzothiazole-2-sulphenamide was established as being at least 1000 mg/kg/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
33 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.37 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Acute/short-term local effects/ Long-term exposure local effects


 


DCBS showed only very slight and transient skin and eye irritation in guideline studies performed according to GLP with rabbits (Monsanto Co. 1985). No classification is required.


 


DCBS was negative in a guinea pig maximization assay (Monsanto Co. 1985). In a read across approach, where physicochemical data and toxicological findings of DCBS, CBS, TBBS and MBS were compared; consistencies in acute toxicity (oral and dermal), skin and eye-irritation, as well as in repeated dose toxicity were found. The substances CBS, TBBS and MBS were all classified as skin sensitizer in humans. Based on this finding and on the similarities noted in toxicity parameter a moderate skin sensitizing potential of DCBS in humans is suggested (Skin Sens. 1B).


 


 


Acute/short-term exposure systemic effects:


The acute toxicity of the test substance DCBS is very low after oral and dermal administration; LD50 values of >5000 mg/kg bw were obtained. Due to the very low oral and dermal acute toxicity of DCBS it is proposed to limit exposure peaks to a factor of 8. This approach is generally in line with the regulatory procedure in Germany (see Technical Rule for Hazardous Substances 900).


 


DNEL short-term systemic oral: 0.37mg/kg bw/day x 8 = 3 mg/kg bw/day


DNEL short-term systemic dermal: 33.3 mg/kg bw/day x 8 = 266.7 mg/kg bw/day


Revision of the risk assessment revealed though that there is no need for these acute DNELs.


 


In three limited inhalation studies with the test substances CBS, TBBS and MBS (Monsanto Co. 1981) exposed rats exhibited occasional nasal irritation which appeared to be concentration related (no more data). These findings were observed immediately after the 6 hour exposure period and disappeared by the next morning. Since the animals recovered from this lesion within 24 hours and these findings could not be correlated to histopathologic effects observed, the observation of nasal irritation in few test substance-exposed animals was not considered to be toxicologically adverse. To cover possible irritating effects no peak exposure factor was added in consistency with DNEL calculations for CBS, TBBS and MBS. For DCBS no additional exposure peak factor is added for the inhalation route.


DNEL short-term systemic inhalation: 1.3 mg/m3 x 1 = 1.3 mg/m3.


Revision of the risk assessment revealed though that there is no need for this acute DNEL.


 


DNEL long-term exposure systemic: Oral:


Several repeated dose studies and reproduction/developmental toxicity studies were performed to evaluate the repeated dose toxicity of DCBS. The consistent finding made in all studies is a reduction of body weight, body weight gain and/or food consumption in treated animals. Overall, a NOAEL of 36.9 mg/kg bw and day is taken for the risk assessment, which based on the findings from the 90-day feeding study (Monsanto Co. 1989).


 


DNEL long-term for oral route


Startpoint: 36.9 mg/kg bw and day 90-day feeding study (Monsanto Co. 1989).


Differences in absorption Abs (oral-rat) / Abs (oral-human): 1


    => Corrected NOAEL 36.9 mg/kg bw/day  


Interspecies differences: Allometric scaling: 4


Remaining interspecies differences: 2.5


 Intraspecies differences: 10


 Differences in duration of exposure (sub- chronic to chronic): 1*


Dose response and endpoint specific/severity issues: 1


Quality of database: 1


 Overall factor (product of individual factors):  100   


 =>general public DNEL long-term for oral route-systemic: 0.37 mg/kg bw/day


* In several repeated dose studies the NOAEL and or LOAEL are in the same range; consistent findings in subacute, subchronic and reproduction/ developmental toxicity studies indicated by a reduction of body weight, body weight gain and/or food consumption.


 


 


General public long-term for dermal route


Startpoint: 2000 mg/kg bw and day subacute dermal toxicity studies in rabbits (read across Monsanto studies CBS, TBBS, MBS 1981)


Differences in absorption Abs (oral-rat) / Abs (dermal-human): 1


=> Corrected NOAEL 2000 mg/kg bw/day


Interspecies differences: Allometric scaling: 2.4


Remaining interspecies differences: 2.5


Intraspecies differences: 10


Differences in duration of exposure (subacute to chronic): 1*


Dose response and endpoint specific/severity issues: 1


Quality of database: 1


Overall factor (product of individual factors): 60


=>General public DNEL long-term for dermal route-systemic: 33.3 mg/kg bw/day


*No specific systemic effects noted for the dermal route, thus a factor of 1 as recommended for the oral route is suggested (the NOAEL and or LOAEL of DCBS are in the same range; consistent findings in subacute, subchronic and reproduction/ developmental toxicity studies indicated by a reduction of body weight, body weight gain and/or food consumption).


 


 


General public long-term for inhalation route


Startpoint: 36.9 mg/kg bw and day 90-day feeding study (Monsanto Co. 1989).


Respiratory volume rat (sRV) general public 1/1.15: 0.87


Differences in absorption Abs (oral-rat) / Abs (inhalation-human): 1


 => Corrected NOAEC 32.1 mg/m3 


Interspecies differences: Allometric scaling: 1


Remaining interspecies differences: 2.5


 Intraspecies differences: 10


 Differences in duration of exposure (sub- chronic to chronic): 1*


Dose response and endpoint specific/severity issues: 1


Quality of database: 1


 Overall factor (product of individual factors):  25 


 =>General public DNEL long-term for inhalation route-systemic: 1.3 mg/m3


* In several repeated dose studies the NOAEL and or LOAEL are in the same range; consistent findings in subacute, subchronic and reproduction/ developmental toxicity studies indicated by a reduction of body weight, body weight gain and/or food consumption.


 


DNEL fertility:


The reproductive toxicity of the test substance DCBS was evaluated in three reproduction/developmental toxicity studies (Ema 2007, 2007b, 2008). In two studies adverse effects on reproduction were noted in treated animals in the range of maternal toxicity. In the reproduction/developmental study (Ema 2007b) adverse effects on reproduction was indicated by a significant lower number of implantations, pups delivered and decreased pup weights at 6000 ppm and 10000 ppm (ca. 476 and 707 mg/kg bw and day in females). These effects are in the range of maternal toxicity, indicated by reduced body weight gain and food consumption at 3000 ppm and higher (ca. 264 mg/kg bw and day). Adverse effects on reproduction was noted in the gavage study (Ema 2007) at 400 mg/kg bw and day in the range of severe maternal toxicity. However, in the two-generation study no significant changes in reproductive indices were noted in any generation even at the highest dose 4500 ppm (ca. 291 mg/kg bw and day). Maternal toxicity was indicated by a reduced body weight, body weight gain and food consumption in F0 females at 4500 ppm. The two-generation study is considered to be the most relevant study. Thus, based on the finding discussed above, the NOAEL fertility (foetal) is 4500 ppm (ca. 291 mg/kg bw and day) and the NOAEL fertility (maternal) is 600 ppm (ca. 54 mg/kg bw and day). Based on the findings of the two-generation study it was concluded that the DNEL long-term exposure systemic covered the DNEL fertility toxicity.


 


DNEL developmental toxicity:


The developmental toxicity of DCBS was evaluated in a repeated dose study with reproduction/developmental toxicity screening test (OECD TG 422; Ema 2007). Severe maternal toxic effects like mortality and clinical signs like decreased body weights, changes in blood chemistry and/or histopathology were noted in dams at 400 mg/kg bw and day. At this dose, all dams lost their litters at delivery or by day 4 of lactation. Thus, the authors concluded, that the NOAEL developmental (maternal/foetal) is 100 mg/kg bw and day. In a two-generation study (OECD TG 416; Ema 2008) no substance-related mortality and clinical signs were noted across generations up to the highest concentration evaluated (ca. 416 mg/kg bw and day in F0 females), whereas reduction of body weight gain in parental animals and offspring was consistently observed throughout the generations in that dose group. The isolated observation of slight delays in preputial separation reported in male offspring and the slight delays in vaginal opening and transient reduced uterus weights in weanling females are of questionable relevance and mainly observed at the toxic dose. Based on the reported decrease in body weight and body weight gain in F1 and F2 offspring, body weight, body weight gain and food consumption in F0 animals at 4500 ppm, the maternal and developmental NOAEL values are 600 ppm (ca. 54 mg/kg bw and day). Based on the findings of the two-generation study it was concluded that the DNEL long-term exposure systemic covered the DNEL for maternal and developmental toxicity.


 


 


In a GLP OECD 414 study eighty-eight mated female New Zealand White rabbits were assigned to four groups of 22 animals each. The test item, N,N-dicyclohexylbenzothiazole-2-sulphenamide, was administered once daily by oral gavage from Days 6 to 28 post-coitum at doses of 100, 300 and 1000 mg/kg/day (Groups 2, 3 and 4, respectively). Rabbits of the control group received the vehicle, 1% aqueous carboxymethyl cellulose with 0.1% Tween-80, alone. Females were checked daily for the presence of clinical signs. Food consumption and body weight were determined at periodic intervals. Formulations prepared on one day during treatment were analyzed for accuracy and homogeneity. On Day 29 post-coitum, all animals were subjected to an examination post-mortem and external, thoracic and abdominal macroscopic findings were recorded. A laparohysterectomy was performed on each female. The uteri, placentae and ovaries were examined, and the numbers of fetuses, early and late resorptions, total implantations and corpora lutea were recorded. Gravid uterine weights were recorded, and net body weights and net body weight changes were calculated. The fetuses were weighed, sexed and examined for external, visceral and skeletal malformations and developmental variations. All live fetuses were euthanized. Approximately, one half of the fetuses were decapitated and the heads were fixed in Bouin’s fixative. All fetuses were dissected and examined for visceral anomalies and subsequently fixed in 96% aqueous ethanol. Following staining with Alizarin Red S, skeletons of all fetuses of all groups were examined.


 


No maternal toxicity and no developmental toxicity was observed in the 100, 300 and 1000 mg/kg/day groups.Based on the results in this prenatal developmental toxicity study in rabbits the maternal and developmental No Observed Adverse Effect Level (NOAEL) for N,N-dicyclohexylbenzothiazole-2-sulphenamide was established as being at least 1000 mg/kg/day.